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From: Arneh Babakhani <ababakha@mc...>  20071209 18:20:01

Hi Everyone, I'm a novice to APBS and am trying to use it to calculate the solvation free energy change for a particular proteinligand complex, and I'd like to compare that result to the solvation energy calculated from Autodock4. [I realize that such a comparison may be invalid, per the differing force fields and methodoligies between APBS and AD4. Nonetheless, I'm curious to see how they compare.] >From my APBS run, I get a solvation free energy of +41.6 kcal/mol . The AD4 solvation free energy term is calculated to be 0.88 kcal/mol. Now again, bearing in mind the obvious differences beween AD4 and APBS, I'm not suprised that these two numbers are differnt. But I am suprised that are VERY different, in both sign and magnitude. Any thoughts or comments? [Notes: I'm only comparing the APBS result with the solvation energy term in the scoring function of AD4. So this AD4 result of 0.88 does NOT include vdw, hbonding, etc. To the best of my understanding, I think AD4 calculates the solvation energy term using an electrostatics approach as well, but one that is vastly different from APBS (it does not solve the PB equation). So I would expect the APBS calculation to be more accurate and closer to "truth".] Thanks, Arneh P.S. Here's what I did in APBS, just so you can check my work. 1. I obtained the Receptor, Ligand, and ReceptorLigand conformations from the AD4 results, converted those into pqr files using the AMBER ff, no problems here. 2. Based off of the tutorial section 5.1 and equation 5.2, and based off of the tool psize.py to judge my dimensions, grid spacing and centeringI exectued the following input file: ## SolvEnergyCalc.in begins here # READ IN MOLECULES read mol pqr Ligand.pqr mol pqr Receptor.pqr mol pqr ReceptorLigandComplex.pqr end elec name solvL # Electrostatics calculation on the solvated state mgmanual # Specify the mode for APBS to run dime 97 97 97 # The grid dimensions nlev 4 # Multigrid level parameter grid 0.33 0.33 0.33 # Grid spacing gcent mol 1 # Center the grid on molecule 1 mol 1 # Perform the calculation on molecule 1 lpbe # Solve the linearized PoissonBoltzmann equation bcfl mdh # Use all multipole moments when calculating the potential pdie 1.0 # Solute dielectric sdie 78.54 # Solvent dielectric chgm spl2 # Splinebased discretization of the delta functions srfm mol # Molecular surface definition srad 1.4 # Solvent probe radius (for molecular surface) swin 0.3 # Solvent surface spline window (not used here) sdens 10.0 # Sphere density for accessibility object temp 298.15 # Temperature calcenergy total # Calculate energies calcforce no # Do not calculate forces end elec name refL # Calculate potential for reference (vacuum) state mgmanual dime 97 97 97 nlev 4 grid 0.33 0.33 0.33 gcent mol 1 mol 1 lpbe bcfl mdh pdie 1.0 sdie 1.0 chgm spl2 srfm mol srad 1.4 swin 0.3 sdens 10.0 temp 298.15 calcenergy total calcforce no end elec name solvR # Electrostatics calculation on the solvated state mgmanual # Specify the mode for APBS to run dime 129 129 129 # The grid dimensions nlev 4 # Multigrid level parameter grid 0.57 0.57 0.57 # Grid spacing gcent 54.783 34.538 28.043 # Center the grid on molecule 2 mol 2 # Perform the calculation on molecule 2 lpbe # Solve the linearized PoissonBoltzmann equation bcfl mdh # Use all multipole moments when calculating the potential pdie 1.0 # Solute dielectric sdie 78.54 # Solvent dielectric chgm spl2 # Splinebased discretization of the delta functions srfm mol # Molecular surface definition srad 1.4 # Solvent probe radius (for molecular surface) swin 0.3 # Solvent surface spline window (not used here) sdens 10.0 # Sphere density for accessibility object temp 298.15 # Temperature calcenergy total # Calculate energies calcforce no # Do not calculate forces end elec name refR # Calculate potential for reference (vacuum) state mgmanual dime 129 129 129 # The grid dimensions nlev 4 # Multigrid level parameter grid 0.57 0.57 0.57 # Grid spacing gcent 54.783 34.538 28.043 # Center the grid on molecule 2 mol 2 lpbe bcfl mdh pdie 1.0 sdie 1.0 chgm spl2 srfm mol srad 1.4 swin 0.3 sdens 10.0 temp 298.15 calcenergy total calcforce no end elec name solvLR # Electrostatics calculation on the solvated state mgmanual # Specify the mode for APBS to run dime 129 129 129 # The grid dimensions nlev 4 # Multigrid level parameter grid 0.57 0.57 0.57 # Grid spacing gcent 54.783 34.538 28.043 # Center the grid on molecule 3 mol 3 # Perform the calculation on molecule 3 lpbe # Solve the linearized PoissonBoltzmann equation bcfl mdh # Use all multipole moments when calculating the potential pdie 1.0 # Solute dielectric sdie 78.54 # Solvent dielectric chgm spl2 # Splinebased discretization of the delta functions srfm mol # Molecular surface definition srad 1.4 # Solvent probe radius (for molecular surface) swin 0.3 # Solvent surface spline window (not used here) sdens 10.0 # Sphere density for accessibility object temp 298.15 # Temperature calcenergy total # Calculate energies calcforce no # Do not calculate forces end elec name refLR # Calculate potential for reference (vacuum) state mgmanual dime 129 129 129 # The grid dimensions nlev 4 # Multigrid level parameter grid 0.57 0.57 0.57 # Grid spacing gcent 54.783 34.538 28.043 # Center the grid on molecule 3 mol 3 lpbe bcfl mdh pdie 1.0 sdie 1.0 chgm spl2 srfm mol srad 1.4 swin 0.3 sdens 10.0 temp 298.15 calcenergy total calcforce no end # Calculate solvation energy print energy solvLR  refLR  solvR + refR  solvL + refL end quit ## SolvEnergyCalc.in ends here The result of which is +1.7407E+02 kJ/mol, which converted into kcal/mol is +41.6. My pqr files are too big to attach here, but if you'd like I can send them to you individually.  Arneh Babakhani McCammon Lab Department of Chemistry & Biochemistry University of California at San Diego 9500 Gilmand Dr MC 0365 La Jolla, CA 920930365 (619)8956540 (858)5344974 (FAX) ababakha@... http://mccammon.ucsd.edu/~ababakha/ 
From: Nathan Baker <baker@cc...>  20071210 13:24:20

Hi Arneh  I'm not particularly familiar with how AutoDock computes their solvation energy terms. However, I do know that PoissonBoltzmann solvation energies are very sensitive to the choice of radii *and* that AMBER radii are meant for explicit solvent calculations  not implicit solvent. With that in mind, it might be interesting to repeat some of these Poisson solvation energies with with Bondi or PARSE radii (where possible) to see how the results differ. Also, as you know, Paul Czodrowski is very familiar with the best parameters for these types of calculations  I'll Cc him on this message to see if he has any additional ideas. Thanks, Nathan On Dec 9, 2007, at 12:19 PM, Arneh Babakhani wrote: > Hi Everyone, > > I'm a novice to APBS and am trying to use it to calculate the > solvation > free energy change for a particular proteinligand complex, and I'd > like > to compare that result to the solvation energy calculated from > Autodock4. > [I realize that such a comparison may be invalid, per the differing > force > fields and methodoligies between APBS and AD4. Nonetheless, I'm > curious > to see how they compare.] > >> From my APBS run, I get a solvation free energy of +41.6 kcal/ >> mol . The > AD4 solvation free energy term is calculated to be 0.88 kcal/mol. > Now > again, bearing in mind the obvious differences beween AD4 and APBS, > I'm > not suprised that these two numbers are differnt. > > But I am suprised that are VERY different, in both sign and magnitude. > Any thoughts or comments? > > [Notes: I'm only comparing the APBS result with the solvation energy > term > in the scoring function of AD4. So this AD4 result of 0.88 does NOT > include vdw, hbonding, etc. To the best of my understanding, I think > AD4 > calculates the solvation energy term using an electrostatics > approach as > well, but one that is vastly different from APBS (it does not solve > the PB > equation). So I would expect the APBS calculation to be more > accurate and > closer to "truth".] > > Thanks, > > Arneh > > P.S. Here's what I did in APBS, just so you can check my work. > > 1. I obtained the Receptor, Ligand, and ReceptorLigand > conformations from > the AD4 results, converted those into pqr files using the AMBER ff, no > problems here. > > 2. Based off of the tutorial section 5.1 and equation 5.2, and based > off > of the tool psize.py to judge my dimensions, grid spacing and > centeringI > exectued the following input file: > > ## SolvEnergyCalc.in begins here > # READ IN MOLECULES > read > mol pqr Ligand.pqr > mol pqr Receptor.pqr > mol pqr ReceptorLigandComplex.pqr > end > > > elec name solvL # Electrostatics calculation on the solvated state > mgmanual # Specify the mode for APBS to run > dime 97 97 97 # The grid dimensions > nlev 4 # Multigrid level parameter > grid 0.33 0.33 0.33 # Grid spacing > gcent mol 1 # Center the grid on molecule 1 > mol 1 # Perform the calculation on molecule 1 > lpbe # Solve the linearized PoissonBoltzmann equation > bcfl mdh # Use all multipole moments when calculating the > potential > pdie 1.0 # Solute dielectric > sdie 78.54 # Solvent dielectric > chgm spl2 # Splinebased discretization of the delta functions > srfm mol # Molecular surface definition > srad 1.4 # Solvent probe radius (for molecular surface) > swin 0.3 # Solvent surface spline window (not used here) > sdens 10.0 # Sphere density for accessibility object > temp 298.15 # Temperature > calcenergy total # Calculate energies > calcforce no # Do not calculate forces > end > > elec name refL # Calculate potential for reference (vacuum) state > mgmanual > dime 97 97 97 > nlev 4 > grid 0.33 0.33 0.33 > gcent mol 1 > mol 1 > lpbe > bcfl mdh > pdie 1.0 > sdie 1.0 > chgm spl2 > srfm mol > srad 1.4 > swin 0.3 > sdens 10.0 > temp 298.15 > calcenergy total > calcforce no > end > > > > > elec name solvR # Electrostatics calculation on the solvated state > mgmanual # Specify the mode for APBS to run > dime 129 129 129 # The grid dimensions > nlev 4 # Multigrid level parameter > grid 0.57 0.57 0.57 # Grid spacing > gcent 54.783 34.538 28.043 # Center the grid on molecule 2 > mol 2 # Perform the calculation on molecule 2 > lpbe # Solve the linearized PoissonBoltzmann equation > bcfl mdh # Use all multipole moments when calculating the > potential > pdie 1.0 # Solute dielectric > sdie 78.54 # Solvent dielectric > chgm spl2 # Splinebased discretization of the delta functions > srfm mol # Molecular surface definition > srad 1.4 # Solvent probe radius (for molecular surface) > swin 0.3 # Solvent surface spline window (not used here) > sdens 10.0 # Sphere density for accessibility object > temp 298.15 # Temperature > calcenergy total # Calculate energies > calcforce no # Do not calculate forces > end > > elec name refR # Calculate potential for reference (vacuum) state > mgmanual > dime 129 129 129 # The grid dimensions > nlev 4 # Multigrid level parameter > grid 0.57 0.57 0.57 # Grid spacing > gcent 54.783 34.538 28.043 # Center the grid on molecule 2 > mol 2 > lpbe > bcfl mdh > pdie 1.0 > sdie 1.0 > chgm spl2 > srfm mol > srad 1.4 > swin 0.3 > sdens 10.0 > temp 298.15 > calcenergy total > calcforce no > end > > > > elec name solvLR # Electrostatics calculation on the solvated state > mgmanual # Specify the mode for APBS to run > dime 129 129 129 # The grid dimensions > nlev 4 # Multigrid level parameter > grid 0.57 0.57 0.57 # Grid spacing > gcent 54.783 34.538 28.043 # Center the grid on molecule 3 > mol 3 # Perform the calculation on molecule 3 > lpbe # Solve the linearized PoissonBoltzmann equation > bcfl mdh # Use all multipole moments when calculating the > potential > pdie 1.0 # Solute dielectric > sdie 78.54 # Solvent dielectric > chgm spl2 # Splinebased discretization of the delta functions > srfm mol # Molecular surface definition > srad 1.4 # Solvent probe radius (for molecular surface) > swin 0.3 # Solvent surface spline window (not used here) > sdens 10.0 # Sphere density for accessibility object > temp 298.15 # Temperature > calcenergy total # Calculate energies > calcforce no # Do not calculate forces > end > > elec name refLR # Calculate potential for reference (vacuum) state > mgmanual > dime 129 129 129 # The grid dimensions > nlev 4 # Multigrid level parameter > grid 0.57 0.57 0.57 # Grid spacing > gcent 54.783 34.538 28.043 # Center the grid on molecule 3 > mol 3 > lpbe > bcfl mdh > pdie 1.0 > sdie 1.0 > chgm spl2 > srfm mol > srad 1.4 > swin 0.3 > sdens 10.0 > temp 298.15 > calcenergy total > calcforce no > end > > # Calculate solvation energy > print energy solvLR  refLR  solvR + refR  solvL + refL end > > quit > > ## SolvEnergyCalc.in ends here > > The result of which is +1.7407E+02 kJ/mol, which converted into kcal/ > mol > is +41.6. > > My pqr files are too big to attach here, but if you'd like I can > send them > to you individually. > > > >  > Arneh Babakhani > McCammon Lab > Department of Chemistry & Biochemistry > University of California at San Diego > 9500 Gilmand Dr MC 0365 > La Jolla, CA 920930365 > (619)8956540 > (858)5344974 (FAX) > ababakha@... > http://mccammon.ucsd.edu/~ababakha/ > < > Ligand > .pqr > > > < > Receptor > .pqr > > > < > ReceptorLigandComplex > .pqr > > >  > SF.Net email is sponsored by: > Check out the new SourceForge.net Marketplace. > It's the best place to buy or sell services for > just about anything Open Source. > http://sourceforge.net/services/buy/index.php_______________________________________________ > apbsusers mailing list > apbsusers@... > https://lists.sourceforge.net/lists/listinfo/apbsusers  Associate Professor, Dept. of Biochemistry and Molecular Biophysics Center for Computational Biology, Washington University in St. Louis Web: http://cholla.wustl.edu/ 
From: Arneh Babakhani <ababakha@mc...>  20071210 14:31:20

Thanks Nathan, I'll give that a shot and post my results, Arneh Nathan Baker wrote: > Hi Arneh  > > I'm not particularly familiar with how AutoDock computes their > solvation energy terms. However, I do know that PoissonBoltzmann > solvation energies are very sensitive to the choice of radii *and* > that AMBER radii are meant for explicit solvent calculations  not > implicit solvent. With that in mind, it might be interesting to repeat > some of these Poisson solvation energies with with Bondi or PARSE > radii (where possible) to see how the results differ. > > Also, as you know, Paul Czodrowski is very familiar with the best > parameters for these types of calculations  I'll Cc him on this > message to see if he has any additional ideas. > > Thanks, > > Nathan > > On Dec 9, 2007, at 12:19 PM, Arneh Babakhani wrote: > >> Hi Everyone, >> >> I'm a novice to APBS and am trying to use it to calculate the solvation >> free energy change for a particular proteinligand complex, and I'd like >> to compare that result to the solvation energy calculated from >> Autodock4. >> [I realize that such a comparison may be invalid, per the differing >> force >> fields and methodoligies between APBS and AD4. Nonetheless, I'm curious >> to see how they compare.] >> >>> From my APBS run, I get a solvation free energy of +41.6 kcal/mol . The >> AD4 solvation free energy term is calculated to be 0.88 kcal/mol. Now >> again, bearing in mind the obvious differences beween AD4 and APBS, I'm >> not suprised that these two numbers are differnt. >> >> But I am suprised that are VERY different, in both sign and magnitude. >> Any thoughts or comments? >> >> [Notes: I'm only comparing the APBS result with the solvation energy >> term >> in the scoring function of AD4. So this AD4 result of 0.88 does NOT >> include vdw, hbonding, etc. To the best of my understanding, I think AD4 >> calculates the solvation energy term using an electrostatics approach as >> well, but one that is vastly different from APBS (it does not solve >> the PB >> equation). So I would expect the APBS calculation to be more accurate >> and >> closer to "truth".] >> >> Thanks, >> >> Arneh >> >> P.S. Here's what I did in APBS, just so you can check my work. >> >> 1. I obtained the Receptor, Ligand, and ReceptorLigand conformations >> from >> the AD4 results, converted those into pqr files using the AMBER ff, no >> problems here. >> >> 2. Based off of the tutorial section 5.1 and equation 5.2, and based off >> of the tool psize.py to judge my dimensions, grid spacing and >> centeringI >> exectued the following input file: >> >> ## SolvEnergyCalc.in begins here >> # READ IN MOLECULES >> read >> mol pqr Ligand.pqr >> mol pqr Receptor.pqr >> mol pqr ReceptorLigandComplex.pqr >> end >> >> >> elec name solvL # Electrostatics calculation on the solvated state >> mgmanual # Specify the mode for APBS to run >> dime 97 97 97 # The grid dimensions >> nlev 4 # Multigrid level parameter >> grid 0.33 0.33 0.33 # Grid spacing >> gcent mol 1 # Center the grid on molecule 1 >> mol 1 # Perform the calculation on molecule 1 >> lpbe # Solve the linearized PoissonBoltzmann equation >> bcfl mdh # Use all multipole moments when calculating the potential >> pdie 1.0 # Solute dielectric >> sdie 78.54 # Solvent dielectric >> chgm spl2 # Splinebased discretization of the delta functions >> srfm mol # Molecular surface definition >> srad 1.4 # Solvent probe radius (for molecular surface) >> swin 0.3 # Solvent surface spline window (not used here) >> sdens 10.0 # Sphere density for accessibility object >> temp 298.15 # Temperature >> calcenergy total # Calculate energies >> calcforce no # Do not calculate forces >> end >> >> elec name refL # Calculate potential for reference (vacuum) state >> mgmanual >> dime 97 97 97 >> nlev 4 >> grid 0.33 0.33 0.33 >> gcent mol 1 >> mol 1 >> lpbe >> bcfl mdh >> pdie 1.0 >> sdie 1.0 >> chgm spl2 >> srfm mol >> srad 1.4 >> swin 0.3 >> sdens 10.0 >> temp 298.15 >> calcenergy total >> calcforce no >> end >> >> >> >> >> elec name solvR # Electrostatics calculation on the solvated state >> mgmanual # Specify the mode for APBS to run >> dime 129 129 129 # The grid dimensions >> nlev 4 # Multigrid level parameter >> grid 0.57 0.57 0.57 # Grid spacing >> gcent 54.783 34.538 28.043 # Center the grid on molecule 2 >> mol 2 # Perform the calculation on molecule 2 >> lpbe # Solve the linearized PoissonBoltzmann equation >> bcfl mdh # Use all multipole moments when calculating the potential >> pdie 1.0 # Solute dielectric >> sdie 78.54 # Solvent dielectric >> chgm spl2 # Splinebased discretization of the delta functions >> srfm mol # Molecular surface definition >> srad 1.4 # Solvent probe radius (for molecular surface) >> swin 0.3 # Solvent surface spline window (not used here) >> sdens 10.0 # Sphere density for accessibility object >> temp 298.15 # Temperature >> calcenergy total # Calculate energies >> calcforce no # Do not calculate forces >> end >> >> elec name refR # Calculate potential for reference (vacuum) state >> mgmanual >> dime 129 129 129 # The grid dimensions >> nlev 4 # Multigrid level parameter >> grid 0.57 0.57 0.57 # Grid spacing >> gcent 54.783 34.538 28.043 # Center the grid on molecule 2 >> mol 2 >> lpbe >> bcfl mdh >> pdie 1.0 >> sdie 1.0 >> chgm spl2 >> srfm mol >> srad 1.4 >> swin 0.3 >> sdens 10.0 >> temp 298.15 >> calcenergy total >> calcforce no >> end >> >> >> >> elec name solvLR # Electrostatics calculation on the solvated state >> mgmanual # Specify the mode for APBS to run >> dime 129 129 129 # The grid dimensions >> nlev 4 # Multigrid level parameter >> grid 0.57 0.57 0.57 # Grid spacing >> gcent 54.783 34.538 28.043 # Center the grid on molecule 3 >> mol 3 # Perform the calculation on molecule 3 >> lpbe # Solve the linearized PoissonBoltzmann equation >> bcfl mdh # Use all multipole moments when calculating the potential >> pdie 1.0 # Solute dielectric >> sdie 78.54 # Solvent dielectric >> chgm spl2 # Splinebased discretization of the delta functions >> srfm mol # Molecular surface definition >> srad 1.4 # Solvent probe radius (for molecular surface) >> swin 0.3 # Solvent surface spline window (not used here) >> sdens 10.0 # Sphere density for accessibility object >> temp 298.15 # Temperature >> calcenergy total # Calculate energies >> calcforce no # Do not calculate forces >> end >> >> elec name refLR # Calculate potential for reference (vacuum) state >> mgmanual >> dime 129 129 129 # The grid dimensions >> nlev 4 # Multigrid level parameter >> grid 0.57 0.57 0.57 # Grid spacing >> gcent 54.783 34.538 28.043 # Center the grid on molecule 3 >> mol 3 >> lpbe >> bcfl mdh >> pdie 1.0 >> sdie 1.0 >> chgm spl2 >> srfm mol >> srad 1.4 >> swin 0.3 >> sdens 10.0 >> temp 298.15 >> calcenergy total >> calcforce no >> end >> >> # Calculate solvation energy >> print energy solvLR  refLR  solvR + refR  solvL + refL end >> >> quit >> >> ## SolvEnergyCalc.in ends here >> >> The result of which is +1.7407E+02 kJ/mol, which converted into kcal/mol >> is +41.6. >> >> My pqr files are too big to attach here, but if you'd like I can send >> them >> to you individually. >> >> >> >> Arneh Babakhani >> McCammon Lab >> Department of Chemistry & Biochemistry >> University of California at San Diego >> 9500 Gilmand Dr MC 0365 >> La Jolla, CA 920930365 >> (619)8956540 >> (858)5344974 (FAX) >> ababakha@... >> http://mccammon.ucsd.edu/~ababakha/ >> <Ligand.pqr><Receptor.pqr><ReceptorLigandComplex.pqr> >> >> SF.Net email is sponsored by: >> Check out the new SourceForge.net Marketplace. >> It's the best place to buy or sell services for >> just about anything Open Source. >> http://sourceforge.net/services/buy/index.php_______________________________________________ >> >> apbsusers mailing list >> apbsusers@... >> https://lists.sourceforge.net/lists/listinfo/apbsusers > >  > Associate Professor, Dept. of Biochemistry and Molecular Biophysics > Center for Computational Biology, Washington University in St. Louis > Web: http://cholla.wustl.edu/ > > >   Arneh Babakhani McCammon Lab Department of Chemistry & Biochemistry University of California at San Diego 9500 Gilmand Dr MC 0365 La Jolla, CA 920930365 (619)8956540 (858)5344974 (FAX) ababakha@... http://mccammon.ucsd.edu/~ababakha/ 
From: Mark Abraham <Mark.A<braham@an...>  20071210 22:59:45

Nathan Baker wrote: > Hi Arneh  > > I'm not particularly familiar with how AutoDock computes their > solvation energy terms. However, I do know that PoissonBoltzmann > solvation energies are very sensitive to the choice of radii *and* > that AMBER radii are meant for explicit solvent calculations  not > implicit solvent. With that in mind, it might be interesting to > repeat some of these Poisson solvation energies with with Bondi or > PARSE radii (where possible) to see how the results differ. A likely source of better PB radii are J MJ Swanson, S A Adcock and J A McCammon (2005). Optimized radii for PoissonBoltzmann calculations with the AMBER force field. In: Journal of Chemical Theory and Computation, 1(3):484493. Mark 
From: Arneh Babakhani <ababakha@mc...>  20071210 23:06:16

Hi Mark, yes, the last result I report from bondi run was using Jess's optimized radii, Arneh Mark Abraham wrote: > Nathan Baker wrote: > >> Hi Arneh  >> >> I'm not particularly familiar with how AutoDock computes their >> solvation energy terms. However, I do know that PoissonBoltzmann >> solvation energies are very sensitive to the choice of radii *and* >> that AMBER radii are meant for explicit solvent calculations  not >> implicit solvent. With that in mind, it might be interesting to >> repeat some of these Poisson solvation energies with with Bondi or >> PARSE radii (where possible) to see how the results differ. >> > > A likely source of better PB radii are > > J MJ Swanson, S A Adcock and J A McCammon (2005). > Optimized radii for PoissonBoltzmann calculations with the AMBER force > field. > In: Journal of Chemical Theory and Computation, 1(3):484493. > > Mark > >  > SF.Net email is sponsored by: > Check out the new SourceForge.net Marketplace. > It's the best place to buy or sell services for > just about anything Open Source. > http://sourceforge.net/services/buy/index.php > _______________________________________________ > apbsusers mailing list > apbsusers@... > https://lists.sourceforge.net/lists/listinfo/apbsusers > >   Arneh Babakhani McCammon Lab Department of Chemistry & Biochemistry University of California at San Diego 9500 Gilmand Dr MC 0365 La Jolla, CA 920930365 (619)8956540 (858)5344974 (FAX) ababakha@... http://mccammon.ucsd.edu/~ababakha/ 
From: Arneh Babakhani <ababakha@mc...>  20071210 18:11:50

Well, using the Amber / Parse / Bondi radii, I get the following values for the calculated solvation energies: 174 / 223 / 190 (kJ mol) so yes, the choice of radii does make a significant difference! I'm exploring the AD4 side of the house to get a better understanding of how their solvation energy is calculated . . . to determine if there's a reasonable way to compare the AD4 and APBS results. I'll post back here again when I figure it out, Arneh Nathan Baker wrote: > Hi Arneh  > > I'm not particularly familiar with how AutoDock computes their > solvation energy terms. However, I do know that PoissonBoltzmann > solvation energies are very sensitive to the choice of radii *and* > that AMBER radii are meant for explicit solvent calculations  not > implicit solvent. With that in mind, it might be interesting to repeat > some of these Poisson solvation energies with with Bondi or PARSE > radii (where possible) to see how the results differ. > > Also, as you know, Paul Czodrowski is very familiar with the best > parameters for these types of calculations  I'll Cc him on this > message to see if he has any additional ideas. > > Thanks, > > Nathan > > On Dec 9, 2007, at 12:19 PM, Arneh Babakhani wrote: > >> Hi Everyone, >> >> I'm a novice to APBS and am trying to use it to calculate the solvation >> free energy change for a particular proteinligand complex, and I'd like >> to compare that result to the solvation energy calculated from >> Autodock4. >> [I realize that such a comparison may be invalid, per the differing >> force >> fields and methodoligies between APBS and AD4. Nonetheless, I'm curious >> to see how they compare.] >> >>> From my APBS run, I get a solvation free energy of +41.6 kcal/mol . The >> AD4 solvation free energy term is calculated to be 0.88 kcal/mol. Now >> again, bearing in mind the obvious differences beween AD4 and APBS, I'm >> not suprised that these two numbers are differnt. >> >> But I am suprised that are VERY different, in both sign and magnitude. >> Any thoughts or comments? >> >> [Notes: I'm only comparing the APBS result with the solvation energy >> term >> in the scoring function of AD4. So this AD4 result of 0.88 does NOT >> include vdw, hbonding, etc. To the best of my understanding, I think AD4 >> calculates the solvation energy term using an electrostatics approach as >> well, but one that is vastly different from APBS (it does not solve >> the PB >> equation). So I would expect the APBS calculation to be more accurate >> and >> closer to "truth".] >> >> Thanks, >> >> Arneh >> >> P.S. Here's what I did in APBS, just so you can check my work. >> >> 1. I obtained the Receptor, Ligand, and ReceptorLigand conformations >> from >> the AD4 results, converted those into pqr files using the AMBER ff, no >> problems here. >> >> 2. Based off of the tutorial section 5.1 and equation 5.2, and based off >> of the tool psize.py to judge my dimensions, grid spacing and >> centeringI >> exectued the following input file: >> >> ## SolvEnergyCalc.in begins here >> # READ IN MOLECULES >> read >> mol pqr Ligand.pqr >> mol pqr Receptor.pqr >> mol pqr ReceptorLigandComplex.pqr >> end >> >> >> elec name solvL # Electrostatics calculation on the solvated state >> mgmanual # Specify the mode for APBS to run >> dime 97 97 97 # The grid dimensions >> nlev 4 # Multigrid level parameter >> grid 0.33 0.33 0.33 # Grid spacing >> gcent mol 1 # Center the grid on molecule 1 >> mol 1 # Perform the calculation on molecule 1 >> lpbe # Solve the linearized PoissonBoltzmann equation >> bcfl mdh # Use all multipole moments when calculating the potential >> pdie 1.0 # Solute dielectric >> sdie 78.54 # Solvent dielectric >> chgm spl2 # Splinebased discretization of the delta functions >> srfm mol # Molecular surface definition >> srad 1.4 # Solvent probe radius (for molecular surface) >> swin 0.3 # Solvent surface spline window (not used here) >> sdens 10.0 # Sphere density for accessibility object >> temp 298.15 # Temperature >> calcenergy total # Calculate energies >> calcforce no # Do not calculate forces >> end >> >> elec name refL # Calculate potential for reference (vacuum) state >> mgmanual >> dime 97 97 97 >> nlev 4 >> grid 0.33 0.33 0.33 >> gcent mol 1 >> mol 1 >> lpbe >> bcfl mdh >> pdie 1.0 >> sdie 1.0 >> chgm spl2 >> srfm mol >> srad 1.4 >> swin 0.3 >> sdens 10.0 >> temp 298.15 >> calcenergy total >> calcforce no >> end >> >> >> >> >> elec name solvR # Electrostatics calculation on the solvated state >> mgmanual # Specify the mode for APBS to run >> dime 129 129 129 # The grid dimensions >> nlev 4 # Multigrid level parameter >> grid 0.57 0.57 0.57 # Grid spacing >> gcent 54.783 34.538 28.043 # Center the grid on molecule 2 >> mol 2 # Perform the calculation on molecule 2 >> lpbe # Solve the linearized PoissonBoltzmann equation >> bcfl mdh # Use all multipole moments when calculating the potential >> pdie 1.0 # Solute dielectric >> sdie 78.54 # Solvent dielectric >> chgm spl2 # Splinebased discretization of the delta functions >> srfm mol # Molecular surface definition >> srad 1.4 # Solvent probe radius (for molecular surface) >> swin 0.3 # Solvent surface spline window (not used here) >> sdens 10.0 # Sphere density for accessibility object >> temp 298.15 # Temperature >> calcenergy total # Calculate energies >> calcforce no # Do not calculate forces >> end >> >> elec name refR # Calculate potential for reference (vacuum) state >> mgmanual >> dime 129 129 129 # The grid dimensions >> nlev 4 # Multigrid level parameter >> grid 0.57 0.57 0.57 # Grid spacing >> gcent 54.783 34.538 28.043 # Center the grid on molecule 2 >> mol 2 >> lpbe >> bcfl mdh >> pdie 1.0 >> sdie 1.0 >> chgm spl2 >> srfm mol >> srad 1.4 >> swin 0.3 >> sdens 10.0 >> temp 298.15 >> calcenergy total >> calcforce no >> end >> >> >> >> elec name solvLR # Electrostatics calculation on the solvated state >> mgmanual # Specify the mode for APBS to run >> dime 129 129 129 # The grid dimensions >> nlev 4 # Multigrid level parameter >> grid 0.57 0.57 0.57 # Grid spacing >> gcent 54.783 34.538 28.043 # Center the grid on molecule 3 >> mol 3 # Perform the calculation on molecule 3 >> lpbe # Solve the linearized PoissonBoltzmann equation >> bcfl mdh # Use all multipole moments when calculating the potential >> pdie 1.0 # Solute dielectric >> sdie 78.54 # Solvent dielectric >> chgm spl2 # Splinebased discretization of the delta functions >> srfm mol # Molecular surface definition >> srad 1.4 # Solvent probe radius (for molecular surface) >> swin 0.3 # Solvent surface spline window (not used here) >> sdens 10.0 # Sphere density for accessibility object >> temp 298.15 # Temperature >> calcenergy total # Calculate energies >> calcforce no # Do not calculate forces >> end >> >> elec name refLR # Calculate potential for reference (vacuum) state >> mgmanual >> dime 129 129 129 # The grid dimensions >> nlev 4 # Multigrid level parameter >> grid 0.57 0.57 0.57 # Grid spacing >> gcent 54.783 34.538 28.043 # Center the grid on molecule 3 >> mol 3 >> lpbe >> bcfl mdh >> pdie 1.0 >> sdie 1.0 >> chgm spl2 >> srfm mol >> srad 1.4 >> swin 0.3 >> sdens 10.0 >> temp 298.15 >> calcenergy total >> calcforce no >> end >> >> # Calculate solvation energy >> print energy solvLR  refLR  solvR + refR  solvL + refL end >> >> quit >> >> ## SolvEnergyCalc.in ends here >> >> The result of which is +1.7407E+02 kJ/mol, which converted into kcal/mol >> is +41.6. >> >> My pqr files are too big to attach here, but if you'd like I can send >> them >> to you individually. >> >> >> >> Arneh Babakhani >> McCammon Lab >> Department of Chemistry & Biochemistry >> University of California at San Diego >> 9500 Gilmand Dr MC 0365 >> La Jolla, CA 920930365 >> (619)8956540 >> (858)5344974 (FAX) >> ababakha@... >> http://mccammon.ucsd.edu/~ababakha/ >> <Ligand.pqr><Receptor.pqr><ReceptorLigandComplex.pqr> >> >> SF.Net email is sponsored by: >> Check out the new SourceForge.net Marketplace. >> It's the best place to buy or sell services for >> just about anything Open Source. >> http://sourceforge.net/services/buy/index.php_______________________________________________ >> >> apbsusers mailing list >> apbsusers@... >> https://lists.sourceforge.net/lists/listinfo/apbsusers > >  > Associate Professor, Dept. of Biochemistry and Molecular Biophysics > Center for Computational Biology, Washington University in St. Louis > Web: http://cholla.wustl.edu/ > > >   Arneh Babakhani McCammon Lab Department of Chemistry & Biochemistry University of California at San Diego 9500 Gilmand Dr MC 0365 La Jolla, CA 920930365 (619)8956540 (858)5344974 (FAX) ababakha@... http://mccammon.ucsd.edu/~ababakha/ 
From: Nathan Baker <baker@cc...>  20071210 18:20:01

Hi Arneh  You also might want to explore your choice of internal dielectric coefficient. Most binding energy calculations with fixed molecular structures use internal dielectric coefficients between 220. Thanks, Nathan On Dec 10, 2007 12:13 PM, Arneh Babakhani <ababakha@...> wrote: > Well, using the Amber / Parse / Bondi radii, I get the following values > for the calculated solvation energies: > > 174 / 223 / 190 (kJ mol) > > so yes, the choice of radii does make a significant difference! I'm > exploring the AD4 side of the house to get a better understanding of how > their solvation energy is calculated . . . to determine if there's a > reasonable way to compare the AD4 and APBS results. I'll post back here > again when I figure it out, > > Arneh > > > > > Nathan Baker wrote: > > Hi Arneh  > > > > I'm not particularly familiar with how AutoDock computes their > > solvation energy terms. However, I do know that PoissonBoltzmann > > solvation energies are very sensitive to the choice of radii *and* > > that AMBER radii are meant for explicit solvent calculations  not > > implicit solvent. With that in mind, it might be interesting to repeat > > some of these Poisson solvation energies with with Bondi or PARSE > > radii (where possible) to see how the results differ. > > > > Also, as you know, Paul Czodrowski is very familiar with the best > > parameters for these types of calculations  I'll Cc him on this > > message to see if he has any additional ideas. > > > > Thanks, > > > > Nathan > > > > On Dec 9, 2007, at 12:19 PM, Arneh Babakhani wrote: > > > >> Hi Everyone, > >> > >> I'm a novice to APBS and am trying to use it to calculate the solvation > >> free energy change for a particular proteinligand complex, and I'd like > >> to compare that result to the solvation energy calculated from > >> Autodock4. > >> [I realize that such a comparison may be invalid, per the differing > >> force > >> fields and methodoligies between APBS and AD4. Nonetheless, I'm curious > >> to see how they compare.] > >> > >>> From my APBS run, I get a solvation free energy of +41.6 kcal/mol . The > >> AD4 solvation free energy term is calculated to be 0.88 kcal/mol. Now > >> again, bearing in mind the obvious differences beween AD4 and APBS, I'm > >> not suprised that these two numbers are differnt. > >> > >> But I am suprised that are VERY different, in both sign and magnitude. > >> Any thoughts or comments? > >> > >> [Notes: I'm only comparing the APBS result with the solvation energy > >> term > >> in the scoring function of AD4. So this AD4 result of 0.88 does NOT > >> include vdw, hbonding, etc. To the best of my understanding, I think AD4 > >> calculates the solvation energy term using an electrostatics approach as > >> well, but one that is vastly different from APBS (it does not solve > >> the PB > >> equation). So I would expect the APBS calculation to be more accurate > >> and > >> closer to "truth".] > >> > >> Thanks, > >> > >> Arneh > >> > >> P.S. Here's what I did in APBS, just so you can check my work. > >> > >> 1. I obtained the Receptor, Ligand, and ReceptorLigand conformations > >> from > >> the AD4 results, converted those into pqr files using the AMBER ff, no > >> problems here. > >> > >> 2. Based off of the tutorial section 5.1 and equation 5.2, and based off > >> of the tool psize.py to judge my dimensions, grid spacing and > >> centeringI > >> exectued the following input file: > >> > >> ## SolvEnergyCalc.in begins here > >> # READ IN MOLECULES > >> read > >> mol pqr Ligand.pqr > >> mol pqr Receptor.pqr > >> mol pqr ReceptorLigandComplex.pqr > >> end > >> > >> > >> elec name solvL # Electrostatics calculation on the solvated state > >> mgmanual # Specify the mode for APBS to run > >> dime 97 97 97 # The grid dimensions > >> nlev 4 # Multigrid level parameter > >> grid 0.33 0.33 0.33 # Grid spacing > >> gcent mol 1 # Center the grid on molecule 1 > >> mol 1 # Perform the calculation on molecule 1 > >> lpbe # Solve the linearized PoissonBoltzmann equation > >> bcfl mdh # Use all multipole moments when calculating the potential > >> pdie 1.0 # Solute dielectric > >> sdie 78.54 # Solvent dielectric > >> chgm spl2 # Splinebased discretization of the delta functions > >> srfm mol # Molecular surface definition > >> srad 1.4 # Solvent probe radius (for molecular surface) > >> swin 0.3 # Solvent surface spline window (not used here) > >> sdens 10.0 # Sphere density for accessibility object > >> temp 298.15 # Temperature > >> calcenergy total # Calculate energies > >> calcforce no # Do not calculate forces > >> end > >> > >> elec name refL # Calculate potential for reference (vacuum) state > >> mgmanual > >> dime 97 97 97 > >> nlev 4 > >> grid 0.33 0.33 0.33 > >> gcent mol 1 > >> mol 1 > >> lpbe > >> bcfl mdh > >> pdie 1.0 > >> sdie 1.0 > >> chgm spl2 > >> srfm mol > >> srad 1.4 > >> swin 0.3 > >> sdens 10.0 > >> temp 298.15 > >> calcenergy total > >> calcforce no > >> end > >> > >> > >> > >> > >> elec name solvR # Electrostatics calculation on the solvated state > >> mgmanual # Specify the mode for APBS to run > >> dime 129 129 129 # The grid dimensions > >> nlev 4 # Multigrid level parameter > >> grid 0.57 0.57 0.57 # Grid spacing > >> gcent 54.783 34.538 28.043 # Center the grid on molecule 2 > >> mol 2 # Perform the calculation on molecule 2 > >> lpbe # Solve the linearized PoissonBoltzmann equation > >> bcfl mdh # Use all multipole moments when calculating the potential > >> pdie 1.0 # Solute dielectric > >> sdie 78.54 # Solvent dielectric > >> chgm spl2 # Splinebased discretization of the delta functions > >> srfm mol # Molecular surface definition > >> srad 1.4 # Solvent probe radius (for molecular surface) > >> swin 0.3 # Solvent surface spline window (not used here) > >> sdens 10.0 # Sphere density for accessibility object > >> temp 298.15 # Temperature > >> calcenergy total # Calculate energies > >> calcforce no # Do not calculate forces > >> end > >> > >> elec name refR # Calculate potential for reference (vacuum) state > >> mgmanual > >> dime 129 129 129 # The grid dimensions > >> nlev 4 # Multigrid level parameter > >> grid 0.57 0.57 0.57 # Grid spacing > >> gcent 54.783 34.538 28.043 # Center the grid on molecule 2 > >> mol 2 > >> lpbe > >> bcfl mdh > >> pdie 1.0 > >> sdie 1.0 > >> chgm spl2 > >> srfm mol > >> srad 1.4 > >> swin 0.3 > >> sdens 10.0 > >> temp 298.15 > >> calcenergy total > >> calcforce no > >> end > >> > >> > >> > >> elec name solvLR # Electrostatics calculation on the solvated state > >> mgmanual # Specify the mode for APBS to run > >> dime 129 129 129 # The grid dimensions > >> nlev 4 # Multigrid level parameter > >> grid 0.57 0.57 0.57 # Grid spacing > >> gcent 54.783 34.538 28.043 # Center the grid on molecule 3 > >> mol 3 # Perform the calculation on molecule 3 > >> lpbe # Solve the linearized PoissonBoltzmann equation > >> bcfl mdh # Use all multipole moments when calculating the potential > >> pdie 1.0 # Solute dielectric > >> sdie 78.54 # Solvent dielectric > >> chgm spl2 # Splinebased discretization of the delta functions > >> srfm mol # Molecular surface definition > >> srad 1.4 # Solvent probe radius (for molecular surface) > >> swin 0.3 # Solvent surface spline window (not used here) > >> sdens 10.0 # Sphere density for accessibility object > >> temp 298.15 # Temperature > >> calcenergy total # Calculate energies > >> calcforce no # Do not calculate forces > >> end > >> > >> elec name refLR # Calculate potential for reference (vacuum) state > >> mgmanual > >> dime 129 129 129 # The grid dimensions > >> nlev 4 # Multigrid level parameter > >> grid 0.57 0.57 0.57 # Grid spacing > >> gcent 54.783 34.538 28.043 # Center the grid on molecule 3 > >> mol 3 > >> lpbe > >> bcfl mdh > >> pdie 1.0 > >> sdie 1.0 > >> chgm spl2 > >> srfm mol > >> srad 1.4 > >> swin 0.3 > >> sdens 10.0 > >> temp 298.15 > >> calcenergy total > >> calcforce no > >> end > >> > >> # Calculate solvation energy > >> print energy solvLR  refLR  solvR + refR  solvL + refL end > >> > >> quit > >> > >> ## SolvEnergyCalc.in ends here > >> > >> The result of which is +1.7407E+02 kJ/mol, which converted into kcal/mol > >> is +41.6. > >> > >> My pqr files are too big to attach here, but if you'd like I can send > >> them > >> to you individually. > >> > >> > >> > >> Arneh Babakhani > >> McCammon Lab > >> Department of Chemistry & Biochemistry > >> University of California at San Diego > >> 9500 Gilmand Dr MC 0365 > >> La Jolla, CA 920930365 > >> (619)8956540 > >> (858)5344974 (FAX) > >> ababakha@... > >> http://mccammon.ucsd.edu/~ababakha/ > >> <Ligand.pqr><Receptor.pqr><ReceptorLigandComplex.pqr> > >> > >> SF.Net email is sponsored by: > >> Check out the new SourceForge.net Marketplace. > >> It's the best place to buy or sell services for > >> just about anything Open Source. > >> http://sourceforge.net/services/buy/index.php_______________________________________________ > >> > >> apbsusers mailing list > >> apbsusers@... > >> https://lists.sourceforge.net/lists/listinfo/apbsusers > > > >  > > Associate Professor, Dept. of Biochemistry and Molecular Biophysics > > Center for Computational Biology, Washington University in St. Louis > > Web: http://cholla.wustl.edu/ > > > > > > > >  >  > Arneh Babakhani > McCammon Lab > Department of Chemistry & Biochemistry > University of California at San Diego > 9500 Gilmand Dr MC 0365 > La Jolla, CA 920930365 > (619)8956540 > (858)5344974 (FAX) > ababakha@... > http://mccammon.ucsd.edu/~ababakha/ > > > >  > SF.Net email is sponsored by: > Check out the new SourceForge.net Marketplace. > It's the best place to buy or sell services for > just about anything Open Source. > http://sourceforge.net/services/buy/index.php > _______________________________________________ > apbsusers mailing list > apbsusers@... > https://lists.sourceforge.net/lists/listinfo/apbsusers >  Associate Professor, Dept. of Biochemistry and Molecular Biophysics Center for Computational Biology, Washington University in St. Louis Web: http://cholla.wustl.edu/ 
From: Arneh Babakhani <ababakha@mc...>  20071212 04:39:38

Well, changing the value of the dielectric does indeed have an effect. For instance, if I set the dielectric of the Ligand = 20, and then I vary the receptor dielectric, using the following values: = 0 / 10 / 20 / 40 / 60 I get an overall delta G of solvation of: = 87.1 / 19.1 / 15.5 / 13.9 / 13.3 kJ/mol. Note, theres not much of a difference between the receptor_dielectric = 40 vs 60 (13.9 vs. 13.3 kj/mol). So I think the calculation has "converged" (for lack of a better word) with respect to my tweaking. Also, this 13.3 kj/mol = 3.18 kcal/mol is more in the ball park with the Autodock result (~ 1 kcal/mol). But of course, this is the result of arbitrarily tweaking the dielectric parameters. I have no real justification for setting the ligand = 20 and the receptor = 60. Arneh > Hi Arneh  > > You also might want to explore your choice of internal dielectric > coefficient. Most binding energy calculations with fixed molecular > structures use internal dielectric coefficients between 220. > > Thanks, > > Nathan > > On Dec 10, 2007 12:13 PM, Arneh Babakhani <ababakha@...> > wrote: >> Well, using the Amber / Parse / Bondi radii, I get the following values >> for the calculated solvation energies: >> >> 174 / 223 / 190 (kJ mol) >> >> so yes, the choice of radii does make a significant difference! I'm >> exploring the AD4 side of the house to get a better understanding of how >> their solvation energy is calculated . . . to determine if there's a >> reasonable way to compare the AD4 and APBS results. I'll post back here >> again when I figure it out, >> >> Arneh >> >> >> >> >> Nathan Baker wrote: >> > Hi Arneh  >> > >> > I'm not particularly familiar with how AutoDock computes their >> > solvation energy terms. However, I do know that PoissonBoltzmann >> > solvation energies are very sensitive to the choice of radii *and* >> > that AMBER radii are meant for explicit solvent calculations  not >> > implicit solvent. With that in mind, it might be interesting to repeat >> > some of these Poisson solvation energies with with Bondi or PARSE >> > radii (where possible) to see how the results differ. >> > >> > Also, as you know, Paul Czodrowski is very familiar with the best >> > parameters for these types of calculations  I'll Cc him on this >> > message to see if he has any additional ideas. >> > >> > Thanks, >> > >> > Nathan >> > >> > On Dec 9, 2007, at 12:19 PM, Arneh Babakhani wrote: >> > >> >> Hi Everyone, >> >> >> >> I'm a novice to APBS and am trying to use it to calculate the >> solvation >> >> free energy change for a particular proteinligand complex, and I'd >> like >> >> to compare that result to the solvation energy calculated from >> >> Autodock4. >> >> [I realize that such a comparison may be invalid, per the differing >> >> force >> >> fields and methodoligies between APBS and AD4. Nonetheless, I'm >> curious >> >> to see how they compare.] >> >> >> >>> From my APBS run, I get a solvation free energy of +41.6 kcal/mol . >> The >> >> AD4 solvation free energy term is calculated to be 0.88 kcal/mol. >> Now >> >> again, bearing in mind the obvious differences beween AD4 and APBS, >> I'm >> >> not suprised that these two numbers are differnt. >> >> >> >> But I am suprised that are VERY different, in both sign and >> magnitude. >> >> Any thoughts or comments? >> >> >> >> [Notes: I'm only comparing the APBS result with the solvation energy >> >> term >> >> in the scoring function of AD4. So this AD4 result of 0.88 does NOT >> >> include vdw, hbonding, etc. To the best of my understanding, I think >> AD4 >> >> calculates the solvation energy term using an electrostatics approach >> as >> >> well, but one that is vastly different from APBS (it does not solve >> >> the PB >> >> equation). So I would expect the APBS calculation to be more accurate >> >> and >> >> closer to "truth".] >> >> >> >> Thanks, >> >> >> >> Arneh >> >> >> >> P.S. Here's what I did in APBS, just so you can check my work. >> >> >> >> 1. I obtained the Receptor, Ligand, and ReceptorLigand conformations >> >> from >> >> the AD4 results, converted those into pqr files using the AMBER ff, >> no >> >> problems here. >> >> >> >> 2. Based off of the tutorial section 5.1 and equation 5.2, and based >> off >> >> of the tool psize.py to judge my dimensions, grid spacing and >> >> centeringI >> >> exectued the following input file: >> >> >> >> ## SolvEnergyCalc.in begins here >> >> # READ IN MOLECULES >> >> read >> >> mol pqr Ligand.pqr >> >> mol pqr Receptor.pqr >> >> mol pqr ReceptorLigandComplex.pqr >> >> end >> >> >> >> >> >> elec name solvL # Electrostatics calculation on the solvated state >> >> mgmanual # Specify the mode for APBS to run >> >> dime 97 97 97 # The grid dimensions >> >> nlev 4 # Multigrid level parameter >> >> grid 0.33 0.33 0.33 # Grid spacing >> >> gcent mol 1 # Center the grid on molecule 1 >> >> mol 1 # Perform the calculation on molecule 1 >> >> lpbe # Solve the linearized PoissonBoltzmann equation >> >> bcfl mdh # Use all multipole moments when calculating the potential >> >> pdie 1.0 # Solute dielectric >> >> sdie 78.54 # Solvent dielectric >> >> chgm spl2 # Splinebased discretization of the delta functions >> >> srfm mol # Molecular surface definition >> >> srad 1.4 # Solvent probe radius (for molecular surface) >> >> swin 0.3 # Solvent surface spline window (not used here) >> >> sdens 10.0 # Sphere density for accessibility object >> >> temp 298.15 # Temperature >> >> calcenergy total # Calculate energies >> >> calcforce no # Do not calculate forces >> >> end >> >> >> >> elec name refL # Calculate potential for reference (vacuum) state >> >> mgmanual >> >> dime 97 97 97 >> >> nlev 4 >> >> grid 0.33 0.33 0.33 >> >> gcent mol 1 >> >> mol 1 >> >> lpbe >> >> bcfl mdh >> >> pdie 1.0 >> >> sdie 1.0 >> >> chgm spl2 >> >> srfm mol >> >> srad 1.4 >> >> swin 0.3 >> >> sdens 10.0 >> >> temp 298.15 >> >> calcenergy total >> >> calcforce no >> >> end >> >> >> >> >> >> >> >> >> >> elec name solvR # Electrostatics calculation on the solvated state >> >> mgmanual # Specify the mode for APBS to run >> >> dime 129 129 129 # The grid dimensions >> >> nlev 4 # Multigrid level parameter >> >> grid 0.57 0.57 0.57 # Grid spacing >> >> gcent 54.783 34.538 28.043 # Center the grid on molecule 2 >> >> mol 2 # Perform the calculation on molecule 2 >> >> lpbe # Solve the linearized PoissonBoltzmann equation >> >> bcfl mdh # Use all multipole moments when calculating the potential >> >> pdie 1.0 # Solute dielectric >> >> sdie 78.54 # Solvent dielectric >> >> chgm spl2 # Splinebased discretization of the delta functions >> >> srfm mol # Molecular surface definition >> >> srad 1.4 # Solvent probe radius (for molecular surface) >> >> swin 0.3 # Solvent surface spline window (not used here) >> >> sdens 10.0 # Sphere density for accessibility object >> >> temp 298.15 # Temperature >> >> calcenergy total # Calculate energies >> >> calcforce no # Do not calculate forces >> >> end >> >> >> >> elec name refR # Calculate potential for reference (vacuum) state >> >> mgmanual >> >> dime 129 129 129 # The grid dimensions >> >> nlev 4 # Multigrid level parameter >> >> grid 0.57 0.57 0.57 # Grid spacing >> >> gcent 54.783 34.538 28.043 # Center the grid on molecule 2 >> >> mol 2 >> >> lpbe >> >> bcfl mdh >> >> pdie 1.0 >> >> sdie 1.0 >> >> chgm spl2 >> >> srfm mol >> >> srad 1.4 >> >> swin 0.3 >> >> sdens 10.0 >> >> temp 298.15 >> >> calcenergy total >> >> calcforce no >> >> end >> >> >> >> >> >> >> >> elec name solvLR # Electrostatics calculation on the solvated state >> >> mgmanual # Specify the mode for APBS to run >> >> dime 129 129 129 # The grid dimensions >> >> nlev 4 # Multigrid level parameter >> >> grid 0.57 0.57 0.57 # Grid spacing >> >> gcent 54.783 34.538 28.043 # Center the grid on molecule 3 >> >> mol 3 # Perform the calculation on molecule 3 >> >> lpbe # Solve the linearized PoissonBoltzmann equation >> >> bcfl mdh # Use all multipole moments when calculating the potential >> >> pdie 1.0 # Solute dielectric >> >> sdie 78.54 # Solvent dielectric >> >> chgm spl2 # Splinebased discretization of the delta functions >> >> srfm mol # Molecular surface definition >> >> srad 1.4 # Solvent probe radius (for molecular surface) >> >> swin 0.3 # Solvent surface spline window (not used here) >> >> sdens 10.0 # Sphere density for accessibility object >> >> temp 298.15 # Temperature >> >> calcenergy total # Calculate energies >> >> calcforce no # Do not calculate forces >> >> end >> >> >> >> elec name refLR # Calculate potential for reference (vacuum) state >> >> mgmanual >> >> dime 129 129 129 # The grid dimensions >> >> nlev 4 # Multigrid level parameter >> >> grid 0.57 0.57 0.57 # Grid spacing >> >> gcent 54.783 34.538 28.043 # Center the grid on molecule 3 >> >> mol 3 >> >> lpbe >> >> bcfl mdh >> >> pdie 1.0 >> >> sdie 1.0 >> >> chgm spl2 >> >> srfm mol >> >> srad 1.4 >> >> swin 0.3 >> >> sdens 10.0 >> >> temp 298.15 >> >> calcenergy total >> >> calcforce no >> >> end >> >> >> >> # Calculate solvation energy >> >> print energy solvLR  refLR  solvR + refR  solvL + refL end >> >> >> >> quit >> >> >> >> ## SolvEnergyCalc.in ends here >> >> >> >> The result of which is +1.7407E+02 kJ/mol, which converted into >> kcal/mol >> >> is +41.6. >> >> >> >> My pqr files are too big to attach here, but if you'd like I can send >> >> them >> >> to you individually. >> >> >> >> >> >> >> >> Arneh Babakhani >> >> McCammon Lab >> >> Department of Chemistry & Biochemistry >> >> University of California at San Diego >> >> 9500 Gilmand Dr MC 0365 >> >> La Jolla, CA 920930365 >> >> (619)8956540 >> >> (858)5344974 (FAX) >> >> ababakha@... >> >> http://mccammon.ucsd.edu/~ababakha/ >> >> <Ligand.pqr><Receptor.pqr><ReceptorLigandComplex.pqr> >> >> >> >> SF.Net email is sponsored by: >> >> Check out the new SourceForge.net Marketplace. >> >> It's the best place to buy or sell services for >> >> just about anything Open Source. >> >> http://sourceforge.net/services/buy/index.php_______________________________________________ >> >> >> >> apbsusers mailing list >> >> apbsusers@... >> >> https://lists.sourceforge.net/lists/listinfo/apbsusers >> > >> >  >> > Associate Professor, Dept. of Biochemistry and Molecular Biophysics >> > Center for Computational Biology, Washington University in St. Louis >> > Web: http://cholla.wustl.edu/ >> > >> > >> > >> >>  >>  >> Arneh Babakhani >> McCammon Lab >> Department of Chemistry & Biochemistry >> University of California at San Diego >> 9500 Gilmand Dr MC 0365 >> La Jolla, CA 920930365 >> (619)8956540 >> (858)5344974 (FAX) >> ababakha@... >> http://mccammon.ucsd.edu/~ababakha/ >> >> >> >>  >> SF.Net email is sponsored by: >> Check out the new SourceForge.net Marketplace. >> It's the best place to buy or sell services for >> just about anything Open Source. >> http://sourceforge.net/services/buy/index.php >> _______________________________________________ >> apbsusers mailing list >> apbsusers@... >> https://lists.sourceforge.net/lists/listinfo/apbsusers >> > > > >  > Associate Professor, Dept. of Biochemistry and Molecular Biophysics > Center for Computational Biology, Washington University in St. Louis > Web: http://cholla.wustl.edu/ >  Arneh Babakhani McCammon Lab Department of Chemistry & Biochemistry University of California at San Diego 9500 Gilmand Dr MC 0365 La Jolla, CA 920930365 (619)8956540 (858)5344974 (FAX) ababakha@... http://mccammon.ucsd.edu/~ababakha/ 
From: Nathan Baker <baker@cc...>  20071213 02:42:42

Hi Arneh  > Well, changing the value of the dielectric does indeed have an effect. > > For instance, if I set the dielectric of the Ligand = 20, and then > I vary > the receptor dielectric, using the following values: > > = 0 / 10 / 20 / 40 / 60 Dielectrics of 40 and 60 seem pretty unreasonable to me. In fact, dielectrics of 20 are generally only invoked when absolutely needed for pKa calculations... > I get an overall delta G of solvation of: > > = 87.1 / 19.1 / 15.5 / 13.9 / 13.3 kJ/mol. > > Note, theres not much of a difference between the > receptor_dielectric = 40 > vs 60 (13.9 vs. 13.3 kj/mol). So I think the calculation has > "converged" > (for lack of a better word) with respect to my tweaking. A crude approximation of dielectric effects on solvation energies is 1/epsi  1/epso where epsi and epso are internal and external dielectrics. It's likely that you're just getting close enough to the solvent dielectric that the energies have stopped changing very much. > Also, this 13.3 kj/mol = 3.18 kcal/mol is more in the ball park with > the > Autodock result (~ 1 kcal/mol). But of course, this is the result of > arbitrarily tweaking the dielectric parameters. I have no real > justification for setting the ligand = 20 and the receptor = 60. Nor do you necessarily have any justification for believing the Autodock result. :) Have you looked at their parameterization references? It might be useful to dig a bit deeper, perhaps starting with molecule that's been studied before with Poisson calculations, and see what Autodock's doing to calculate solvation energies. Thanks, Nathan > > Arneh > > > > > >> Hi Arneh  >> >> You also might want to explore your choice of internal dielectric >> coefficient. Most binding energy calculations with fixed molecular >> structures use internal dielectric coefficients between 220. >> >> Thanks, >> >> Nathan >> >> On Dec 10, 2007 12:13 PM, Arneh Babakhani >> <ababakha@...> >> wrote: >>> Well, using the Amber / Parse / Bondi radii, I get the following >>> values >>> for the calculated solvation energies: >>> >>> 174 / 223 / 190 (kJ mol) >>> >>> so yes, the choice of radii does make a significant difference! I'm >>> exploring the AD4 side of the house to get a better understanding >>> of how >>> their solvation energy is calculated . . . to determine if there's a >>> reasonable way to compare the AD4 and APBS results. I'll post back >>> here >>> again when I figure it out, >>> >>> Arneh >>> >>> >>> >>> >>> Nathan Baker wrote: >>>> Hi Arneh  >>>> >>>> I'm not particularly familiar with how AutoDock computes their >>>> solvation energy terms. However, I do know that PoissonBoltzmann >>>> solvation energies are very sensitive to the choice of radii *and* >>>> that AMBER radii are meant for explicit solvent calculations  not >>>> implicit solvent. With that in mind, it might be interesting to >>>> repeat >>>> some of these Poisson solvation energies with with Bondi or PARSE >>>> radii (where possible) to see how the results differ. >>>> >>>> Also, as you know, Paul Czodrowski is very familiar with the best >>>> parameters for these types of calculations  I'll Cc him on this >>>> message to see if he has any additional ideas. >>>> >>>> Thanks, >>>> >>>> Nathan >>>> >>>> On Dec 9, 2007, at 12:19 PM, Arneh Babakhani wrote: >>>> >>>>> Hi Everyone, >>>>> >>>>> I'm a novice to APBS and am trying to use it to calculate the >>> solvation >>>>> free energy change for a particular proteinligand complex, and >>>>> I'd >>> like >>>>> to compare that result to the solvation energy calculated from >>>>> Autodock4. >>>>> [I realize that such a comparison may be invalid, per the >>>>> differing >>>>> force >>>>> fields and methodoligies between APBS and AD4. Nonetheless, I'm >>> curious >>>>> to see how they compare.] >>>>> >>>>>> From my APBS run, I get a solvation free energy of +41.6 kcal/ >>>>>> mol . >>> The >>>>> AD4 solvation free energy term is calculated to be 0.88 kcal/mol. >>> Now >>>>> again, bearing in mind the obvious differences beween AD4 and >>>>> APBS, >>> I'm >>>>> not suprised that these two numbers are differnt. >>>>> >>>>> But I am suprised that are VERY different, in both sign and >>> magnitude. >>>>> Any thoughts or comments? >>>>> >>>>> [Notes: I'm only comparing the APBS result with the solvation >>>>> energy >>>>> term >>>>> in the scoring function of AD4. So this AD4 result of 0.88 does >>>>> NOT >>>>> include vdw, hbonding, etc. To the best of my understanding, I >>>>> think >>> AD4 >>>>> calculates the solvation energy term using an electrostatics >>>>> approach >>> as >>>>> well, but one that is vastly different from APBS (it does not >>>>> solve >>>>> the PB >>>>> equation). So I would expect the APBS calculation to be more >>>>> accurate >>>>> and >>>>> closer to "truth".] >>>>> >>>>> Thanks, >>>>> >>>>> Arneh >>>>> >>>>> P.S. Here's what I did in APBS, just so you can check my work. >>>>> >>>>> 1. I obtained the Receptor, Ligand, and ReceptorLigand >>>>> conformations >>>>> from >>>>> the AD4 results, converted those into pqr files using the AMBER >>>>> ff, >>> no >>>>> problems here. >>>>> >>>>> 2. Based off of the tutorial section 5.1 and equation 5.2, and >>>>> based >>> off >>>>> of the tool psize.py to judge my dimensions, grid spacing and >>>>> centeringI >>>>> exectued the following input file: >>>>> >>>>> ## SolvEnergyCalc.in begins here >>>>> # READ IN MOLECULES >>>>> read >>>>> mol pqr Ligand.pqr >>>>> mol pqr Receptor.pqr >>>>> mol pqr ReceptorLigandComplex.pqr >>>>> end >>>>> >>>>> >>>>> elec name solvL # Electrostatics calculation on the solvated state >>>>> mgmanual # Specify the mode for APBS to run >>>>> dime 97 97 97 # The grid dimensions >>>>> nlev 4 # Multigrid level parameter >>>>> grid 0.33 0.33 0.33 # Grid spacing >>>>> gcent mol 1 # Center the grid on molecule 1 >>>>> mol 1 # Perform the calculation on molecule 1 >>>>> lpbe # Solve the linearized PoissonBoltzmann equation >>>>> bcfl mdh # Use all multipole moments when calculating the >>>>> potential >>>>> pdie 1.0 # Solute dielectric >>>>> sdie 78.54 # Solvent dielectric >>>>> chgm spl2 # Splinebased discretization of the delta functions >>>>> srfm mol # Molecular surface definition >>>>> srad 1.4 # Solvent probe radius (for molecular surface) >>>>> swin 0.3 # Solvent surface spline window (not used here) >>>>> sdens 10.0 # Sphere density for accessibility object >>>>> temp 298.15 # Temperature >>>>> calcenergy total # Calculate energies >>>>> calcforce no # Do not calculate forces >>>>> end >>>>> >>>>> elec name refL # Calculate potential for reference (vacuum) state >>>>> mgmanual >>>>> dime 97 97 97 >>>>> nlev 4 >>>>> grid 0.33 0.33 0.33 >>>>> gcent mol 1 >>>>> mol 1 >>>>> lpbe >>>>> bcfl mdh >>>>> pdie 1.0 >>>>> sdie 1.0 >>>>> chgm spl2 >>>>> srfm mol >>>>> srad 1.4 >>>>> swin 0.3 >>>>> sdens 10.0 >>>>> temp 298.15 >>>>> calcenergy total >>>>> calcforce no >>>>> end >>>>> >>>>> >>>>> >>>>> >>>>> elec name solvR # Electrostatics calculation on the solvated state >>>>> mgmanual # Specify the mode for APBS to run >>>>> dime 129 129 129 # The grid dimensions >>>>> nlev 4 # Multigrid level parameter >>>>> grid 0.57 0.57 0.57 # Grid spacing >>>>> gcent 54.783 34.538 28.043 # Center the grid on molecule 2 >>>>> mol 2 # Perform the calculation on molecule 2 >>>>> lpbe # Solve the linearized PoissonBoltzmann equation >>>>> bcfl mdh # Use all multipole moments when calculating the >>>>> potential >>>>> pdie 1.0 # Solute dielectric >>>>> sdie 78.54 # Solvent dielectric >>>>> chgm spl2 # Splinebased discretization of the delta functions >>>>> srfm mol # Molecular surface definition >>>>> srad 1.4 # Solvent probe radius (for molecular surface) >>>>> swin 0.3 # Solvent surface spline window (not used here) >>>>> sdens 10.0 # Sphere density for accessibility object >>>>> temp 298.15 # Temperature >>>>> calcenergy total # Calculate energies >>>>> calcforce no # Do not calculate forces >>>>> end >>>>> >>>>> elec name refR # Calculate potential for reference (vacuum) state >>>>> mgmanual >>>>> dime 129 129 129 # The grid dimensions >>>>> nlev 4 # Multigrid level parameter >>>>> grid 0.57 0.57 0.57 # Grid spacing >>>>> gcent 54.783 34.538 28.043 # Center the grid on molecule 2 >>>>> mol 2 >>>>> lpbe >>>>> bcfl mdh >>>>> pdie 1.0 >>>>> sdie 1.0 >>>>> chgm spl2 >>>>> srfm mol >>>>> srad 1.4 >>>>> swin 0.3 >>>>> sdens 10.0 >>>>> temp 298.15 >>>>> calcenergy total >>>>> calcforce no >>>>> end >>>>> >>>>> >>>>> >>>>> elec name solvLR # Electrostatics calculation on the solvated >>>>> state >>>>> mgmanual # Specify the mode for APBS to run >>>>> dime 129 129 129 # The grid dimensions >>>>> nlev 4 # Multigrid level parameter >>>>> grid 0.57 0.57 0.57 # Grid spacing >>>>> gcent 54.783 34.538 28.043 # Center the grid on molecule 3 >>>>> mol 3 # Perform the calculation on molecule 3 >>>>> lpbe # Solve the linearized PoissonBoltzmann equation >>>>> bcfl mdh # Use all multipole moments when calculating the >>>>> potential >>>>> pdie 1.0 # Solute dielectric >>>>> sdie 78.54 # Solvent dielectric >>>>> chgm spl2 # Splinebased discretization of the delta functions >>>>> srfm mol # Molecular surface definition >>>>> srad 1.4 # Solvent probe radius (for molecular surface) >>>>> swin 0.3 # Solvent surface spline window (not used here) >>>>> sdens 10.0 # Sphere density for accessibility object >>>>> temp 298.15 # Temperature >>>>> calcenergy total # Calculate energies >>>>> calcforce no # Do not calculate forces >>>>> end >>>>> >>>>> elec name refLR # Calculate potential for reference (vacuum) state >>>>> mgmanual >>>>> dime 129 129 129 # The grid dimensions >>>>> nlev 4 # Multigrid level parameter >>>>> grid 0.57 0.57 0.57 # Grid spacing >>>>> gcent 54.783 34.538 28.043 # Center the grid on molecule 3 >>>>> mol 3 >>>>> lpbe >>>>> bcfl mdh >>>>> pdie 1.0 >>>>> sdie 1.0 >>>>> chgm spl2 >>>>> srfm mol >>>>> srad 1.4 >>>>> swin 0.3 >>>>> sdens 10.0 >>>>> temp 298.15 >>>>> calcenergy total >>>>> calcforce no >>>>> end >>>>> >>>>> # Calculate solvation energy >>>>> print energy solvLR  refLR  solvR + refR  solvL + refL end >>>>> >>>>> quit >>>>> >>>>> ## SolvEnergyCalc.in ends here >>>>> >>>>> The result of which is +1.7407E+02 kJ/mol, which converted into >>> kcal/mol >>>>> is +41.6. >>>>> >>>>> My pqr files are too big to attach here, but if you'd like I can >>>>> send >>>>> them >>>>> to you individually. >>>>> >>>>> >>>>> >>>>> Arneh Babakhani >>>>> McCammon Lab >>>>> Department of Chemistry & Biochemistry >>>>> University of California at San Diego >>>>> 9500 Gilmand Dr MC 0365 >>>>> La Jolla, CA 920930365 >>>>> (619)8956540 >>>>> (858)5344974 (FAX) >>>>> ababakha@... >>>>> http://mccammon.ucsd.edu/~ababakha/ >>>>> < >>>>> Ligand >>>>> .pqr >>>>> > >>>>> < >>>>> Receptor >>>>> .pqr >>>>> > >>>>> < >>>>> ReceptorLigandComplex >>>>> .pqr >>>>> > >>>>>  >>>>> >>>>> SF.Net email is sponsored by: >>>>> Check out the new SourceForge.net Marketplace. >>>>> It's the best place to buy or sell services for >>>>> just about anything Open Source. >>>>> http://sourceforge.net/services/buy/index.php_______________________________________________ >>>>> >>>>> apbsusers mailing list >>>>> apbsusers@... >>>>> https://lists.sourceforge.net/lists/listinfo/apbsusers >>>> >>>>  >>>> Associate Professor, Dept. of Biochemistry and Molecular Biophysics >>>> Center for Computational Biology, Washington University in St. >>>> Louis >>>> Web: http://cholla.wustl.edu/ >>>> >>>> >>>> >>> >>>  >>>  >>> Arneh Babakhani >>> McCammon Lab >>> Department of Chemistry & Biochemistry >>> University of California at San Diego >>> 9500 Gilmand Dr MC 0365 >>> La Jolla, CA 920930365 >>> (619)8956540 >>> (858)5344974 (FAX) >>> ababakha@... >>> http://mccammon.ucsd.edu/~ababakha/ >>> >>> >>> >>>  >>> SF.Net email is sponsored by: >>> Check out the new SourceForge.net Marketplace. >>> It's the best place to buy or sell services for >>> just about anything Open Source. >>> http://sourceforge.net/services/buy/index.php >>> _______________________________________________ >>> apbsusers mailing list >>> apbsusers@... >>> https://lists.sourceforge.net/lists/listinfo/apbsusers >>> >> >> >> >>  >> Associate Professor, Dept. of Biochemistry and Molecular Biophysics >> Center for Computational Biology, Washington University in St. Louis >> Web: http://cholla.wustl.edu/ >> > > >  > Arneh Babakhani > McCammon Lab > Department of Chemistry & Biochemistry > University of California at San Diego > 9500 Gilmand Dr MC 0365 > La Jolla, CA 920930365 > (619)8956540 > (858)5344974 (FAX) > ababakha@... > http://mccammon.ucsd.edu/~ababakha/ > > >  > SF.Net email is sponsored by: > Check out the new SourceForge.net Marketplace. > It's the best place to buy or sell services for > just about anything Open Source. > http://sourceforge.net/services/buy/index.php > _______________________________________________ > apbsusers mailing list > apbsusers@... > https://lists.sourceforge.net/lists/listinfo/apbsusers  Associate Professor, Dept. of Biochemistry and Molecular Biophysics Center for Computational Biology, Washington University in St. Louis Web: http://cholla.wustl.edu/ 
From: Arneh Babakhani <ababakha@mc...>  20071213 03:02:28

Yes, very true. I have looked at the AD references and am presently looking at the actual AD code, to try and understand exactly how the solvation term in the scoring function is calculated. Will keep you all posted, thanks for the help, its nice to have an active mailing list! Arneh > Hi Arneh  > >> Well, changing the value of the dielectric does indeed have an effect. >> >> For instance, if I set the dielectric of the Ligand = 20, and then >> I vary >> the receptor dielectric, using the following values: >> >> = 0 / 10 / 20 / 40 / 60 > > Dielectrics of 40 and 60 seem pretty unreasonable to me. In fact, > dielectrics of 20 are generally only invoked when absolutely needed > for pKa calculations... > >> I get an overall delta G of solvation of: >> >> = 87.1 / 19.1 / 15.5 / 13.9 / 13.3 kJ/mol. >> >> Note, theres not much of a difference between the >> receptor_dielectric = 40 >> vs 60 (13.9 vs. 13.3 kj/mol). So I think the calculation has >> "converged" >> (for lack of a better word) with respect to my tweaking. > > A crude approximation of dielectric effects on solvation energies is > > 1/epsi  1/epso > > where epsi and epso are internal and external dielectrics. It's > likely that you're just getting close enough to the solvent dielectric > that the energies have stopped changing very much. > >> Also, this 13.3 kj/mol = 3.18 kcal/mol is more in the ball park with >> the >> Autodock result (~ 1 kcal/mol). But of course, this is the result of >> arbitrarily tweaking the dielectric parameters. I have no real >> justification for setting the ligand = 20 and the receptor = 60. > > Nor do you necessarily have any justification for believing the > Autodock result. :) Have you looked at their parameterization > references? It might be useful to dig a bit deeper, perhaps starting > with molecule that's been studied before with Poisson calculations, > and see what Autodock's doing to calculate solvation energies. > > Thanks, > > Nathan > > >> >> Arneh >> >> >> >> >> >>> Hi Arneh  >>> >>> You also might want to explore your choice of internal dielectric >>> coefficient. Most binding energy calculations with fixed molecular >>> structures use internal dielectric coefficients between 220. >>> >>> Thanks, >>> >>> Nathan >>> >>> On Dec 10, 2007 12:13 PM, Arneh Babakhani >>> <ababakha@...> >>> wrote: >>>> Well, using the Amber / Parse / Bondi radii, I get the following >>>> values >>>> for the calculated solvation energies: >>>> >>>> 174 / 223 / 190 (kJ mol) >>>> >>>> so yes, the choice of radii does make a significant difference! I'm >>>> exploring the AD4 side of the house to get a better understanding >>>> of how >>>> their solvation energy is calculated . . . to determine if there's a >>>> reasonable way to compare the AD4 and APBS results. I'll post back >>>> here >>>> again when I figure it out, >>>> >>>> Arneh >>>> >>>> >>>> >>>> >>>> Nathan Baker wrote: >>>>> Hi Arneh  >>>>> >>>>> I'm not particularly familiar with how AutoDock computes their >>>>> solvation energy terms. However, I do know that PoissonBoltzmann >>>>> solvation energies are very sensitive to the choice of radii *and* >>>>> that AMBER radii are meant for explicit solvent calculations  not >>>>> implicit solvent. With that in mind, it might be interesting to >>>>> repeat >>>>> some of these Poisson solvation energies with with Bondi or PARSE >>>>> radii (where possible) to see how the results differ. >>>>> >>>>> Also, as you know, Paul Czodrowski is very familiar with the best >>>>> parameters for these types of calculations  I'll Cc him on this >>>>> message to see if he has any additional ideas. >>>>> >>>>> Thanks, >>>>> >>>>> Nathan >>>>> >>>>> On Dec 9, 2007, at 12:19 PM, Arneh Babakhani wrote: >>>>> >>>>>> Hi Everyone, >>>>>> >>>>>> I'm a novice to APBS and am trying to use it to calculate the >>>> solvation >>>>>> free energy change for a particular proteinligand complex, and >>>>>> I'd >>>> like >>>>>> to compare that result to the solvation energy calculated from >>>>>> Autodock4. >>>>>> [I realize that such a comparison may be invalid, per the >>>>>> differing >>>>>> force >>>>>> fields and methodoligies between APBS and AD4. Nonetheless, I'm >>>> curious >>>>>> to see how they compare.] >>>>>> >>>>>>> From my APBS run, I get a solvation free energy of +41.6 kcal/ >>>>>>> mol . >>>> The >>>>>> AD4 solvation free energy term is calculated to be 0.88 kcal/mol. >>>> Now >>>>>> again, bearing in mind the obvious differences beween AD4 and >>>>>> APBS, >>>> I'm >>>>>> not suprised that these two numbers are differnt. >>>>>> >>>>>> But I am suprised that are VERY different, in both sign and >>>> magnitude. >>>>>> Any thoughts or comments? >>>>>> >>>>>> [Notes: I'm only comparing the APBS result with the solvation >>>>>> energy >>>>>> term >>>>>> in the scoring function of AD4. So this AD4 result of 0.88 does >>>>>> NOT >>>>>> include vdw, hbonding, etc. To the best of my understanding, I >>>>>> think >>>> AD4 >>>>>> calculates the solvation energy term using an electrostatics >>>>>> approach >>>> as >>>>>> well, but one that is vastly different from APBS (it does not >>>>>> solve >>>>>> the PB >>>>>> equation). So I would expect the APBS calculation to be more >>>>>> accurate >>>>>> and >>>>>> closer to "truth".] >>>>>> >>>>>> Thanks, >>>>>> >>>>>> Arneh >>>>>> >>>>>> P.S. Here's what I did in APBS, just so you can check my work. >>>>>> >>>>>> 1. I obtained the Receptor, Ligand, and ReceptorLigand >>>>>> conformations >>>>>> from >>>>>> the AD4 results, converted those into pqr files using the AMBER >>>>>> ff, >>>> no >>>>>> problems here. >>>>>> >>>>>> 2. Based off of the tutorial section 5.1 and equation 5.2, and >>>>>> based >>>> off >>>>>> of the tool psize.py to judge my dimensions, grid spacing and >>>>>> centeringI >>>>>> exectued the following input file: >>>>>> >>>>>> ## SolvEnergyCalc.in begins here >>>>>> # READ IN MOLECULES >>>>>> read >>>>>> mol pqr Ligand.pqr >>>>>> mol pqr Receptor.pqr >>>>>> mol pqr ReceptorLigandComplex.pqr >>>>>> end >>>>>> >>>>>> >>>>>> elec name solvL # Electrostatics calculation on the solvated state >>>>>> mgmanual # Specify the mode for APBS to run >>>>>> dime 97 97 97 # The grid dimensions >>>>>> nlev 4 # Multigrid level parameter >>>>>> grid 0.33 0.33 0.33 # Grid spacing >>>>>> gcent mol 1 # Center the grid on molecule 1 >>>>>> mol 1 # Perform the calculation on molecule 1 >>>>>> lpbe # Solve the linearized PoissonBoltzmann equation >>>>>> bcfl mdh # Use all multipole moments when calculating the >>>>>> potential >>>>>> pdie 1.0 # Solute dielectric >>>>>> sdie 78.54 # Solvent dielectric >>>>>> chgm spl2 # Splinebased discretization of the delta functions >>>>>> srfm mol # Molecular surface definition >>>>>> srad 1.4 # Solvent probe radius (for molecular surface) >>>>>> swin 0.3 # Solvent surface spline window (not used here) >>>>>> sdens 10.0 # Sphere density for accessibility object >>>>>> temp 298.15 # Temperature >>>>>> calcenergy total # Calculate energies >>>>>> calcforce no # Do not calculate forces >>>>>> end >>>>>> >>>>>> elec name refL # Calculate potential for reference (vacuum) state >>>>>> mgmanual >>>>>> dime 97 97 97 >>>>>> nlev 4 >>>>>> grid 0.33 0.33 0.33 >>>>>> gcent mol 1 >>>>>> mol 1 >>>>>> lpbe >>>>>> bcfl mdh >>>>>> pdie 1.0 >>>>>> sdie 1.0 >>>>>> chgm spl2 >>>>>> srfm mol >>>>>> srad 1.4 >>>>>> swin 0.3 >>>>>> sdens 10.0 >>>>>> temp 298.15 >>>>>> calcenergy total >>>>>> calcforce no >>>>>> end >>>>>> >>>>>> >>>>>> >>>>>> >>>>>> elec name solvR # Electrostatics calculation on the solvated state >>>>>> mgmanual # Specify the mode for APBS to run >>>>>> dime 129 129 129 # The grid dimensions >>>>>> nlev 4 # Multigrid level parameter >>>>>> grid 0.57 0.57 0.57 # Grid spacing >>>>>> gcent 54.783 34.538 28.043 # Center the grid on molecule 2 >>>>>> mol 2 # Perform the calculation on molecule 2 >>>>>> lpbe # Solve the linearized PoissonBoltzmann equation >>>>>> bcfl mdh # Use all multipole moments when calculating the >>>>>> potential >>>>>> pdie 1.0 # Solute dielectric >>>>>> sdie 78.54 # Solvent dielectric >>>>>> chgm spl2 # Splinebased discretization of the delta functions >>>>>> srfm mol # Molecular surface definition >>>>>> srad 1.4 # Solvent probe radius (for molecular surface) >>>>>> swin 0.3 # Solvent surface spline window (not used here) >>>>>> sdens 10.0 # Sphere density for accessibility object >>>>>> temp 298.15 # Temperature >>>>>> calcenergy total # Calculate energies >>>>>> calcforce no # Do not calculate forces >>>>>> end >>>>>> >>>>>> elec name refR # Calculate potential for reference (vacuum) state >>>>>> mgmanual >>>>>> dime 129 129 129 # The grid dimensions >>>>>> nlev 4 # Multigrid level parameter >>>>>> grid 0.57 0.57 0.57 # Grid spacing >>>>>> gcent 54.783 34.538 28.043 # Center the grid on molecule 2 >>>>>> mol 2 >>>>>> lpbe >>>>>> bcfl mdh >>>>>> pdie 1.0 >>>>>> sdie 1.0 >>>>>> chgm spl2 >>>>>> srfm mol >>>>>> srad 1.4 >>>>>> swin 0.3 >>>>>> sdens 10.0 >>>>>> temp 298.15 >>>>>> calcenergy total >>>>>> calcforce no >>>>>> end >>>>>> >>>>>> >>>>>> >>>>>> elec name solvLR # Electrostatics calculation on the solvated >>>>>> state >>>>>> mgmanual # Specify the mode for APBS to run >>>>>> dime 129 129 129 # The grid dimensions >>>>>> nlev 4 # Multigrid level parameter >>>>>> grid 0.57 0.57 0.57 # Grid spacing >>>>>> gcent 54.783 34.538 28.043 # Center the grid on molecule 3 >>>>>> mol 3 # Perform the calculation on molecule 3 >>>>>> lpbe # Solve the linearized PoissonBoltzmann equation >>>>>> bcfl mdh # Use all multipole moments when calculating the >>>>>> potential >>>>>> pdie 1.0 # Solute dielectric >>>>>> sdie 78.54 # Solvent dielectric >>>>>> chgm spl2 # Splinebased discretization of the delta functions >>>>>> srfm mol # Molecular surface definition >>>>>> srad 1.4 # Solvent probe radius (for molecular surface) >>>>>> swin 0.3 # Solvent surface spline window (not used here) >>>>>> sdens 10.0 # Sphere density for accessibility object >>>>>> temp 298.15 # Temperature >>>>>> calcenergy total # Calculate energies >>>>>> calcforce no # Do not calculate forces >>>>>> end >>>>>> >>>>>> elec name refLR # Calculate potential for reference (vacuum) state >>>>>> mgmanual >>>>>> dime 129 129 129 # The grid dimensions >>>>>> nlev 4 # Multigrid level parameter >>>>>> grid 0.57 0.57 0.57 # Grid spacing >>>>>> gcent 54.783 34.538 28.043 # Center the grid on molecule 3 >>>>>> mol 3 >>>>>> lpbe >>>>>> bcfl mdh >>>>>> pdie 1.0 >>>>>> sdie 1.0 >>>>>> chgm spl2 >>>>>> srfm mol >>>>>> srad 1.4 >>>>>> swin 0.3 >>>>>> sdens 10.0 >>>>>> temp 298.15 >>>>>> calcenergy total >>>>>> calcforce no >>>>>> end >>>>>> >>>>>> # Calculate solvation energy >>>>>> print energy solvLR  refLR  solvR + refR  solvL + refL end >>>>>> >>>>>> quit >>>>>> >>>>>> ## SolvEnergyCalc.in ends here >>>>>> >>>>>> The result of which is +1.7407E+02 kJ/mol, which converted into >>>> kcal/mol >>>>>> is +41.6. >>>>>> >>>>>> My pqr files are too big to attach here, but if you'd like I can >>>>>> send >>>>>> them >>>>>> to you individually. >>>>>> >>>>>> >>>>>> >>>>>> Arneh Babakhani >>>>>> McCammon Lab >>>>>> Department of Chemistry & Biochemistry >>>>>> University of California at San Diego >>>>>> 9500 Gilmand Dr MC 0365 >>>>>> La Jolla, CA 920930365 >>>>>> (619)8956540 >>>>>> (858)5344974 (FAX) >>>>>> ababakha@... >>>>>> http://mccammon.ucsd.edu/~ababakha/ >>>>>> < >>>>>> Ligand >>>>>> .pqr >>>>>> > >>>>>> < >>>>>> Receptor >>>>>> .pqr >>>>>> > >>>>>> < >>>>>> ReceptorLigandComplex >>>>>> .pqr >>>>>> > >>>>>>  >>>>>> >>>>>> SF.Net email is sponsored by: >>>>>> Check out the new SourceForge.net Marketplace. >>>>>> It's the best place to buy or sell services for >>>>>> just about anything Open Source. >>>>>> http://sourceforge.net/services/buy/index.php_______________________________________________ >>>>>> >>>>>> apbsusers mailing list >>>>>> apbsusers@... >>>>>> https://lists.sourceforge.net/lists/listinfo/apbsusers >>>>> >>>>>  >>>>> Associate Professor, Dept. of Biochemistry and Molecular Biophysics >>>>> Center for Computational Biology, Washington University in St. >>>>> Louis >>>>> Web: http://cholla.wustl.edu/ >>>>> >>>>> >>>>> >>>> >>>>  >>>>  >>>> Arneh Babakhani >>>> McCammon Lab >>>> Department of Chemistry & Biochemistry >>>> University of California at San Diego >>>> 9500 Gilmand Dr MC 0365 >>>> La Jolla, CA 920930365 >>>> (619)8956540 >>>> (858)5344974 (FAX) >>>> ababakha@... >>>> http://mccammon.ucsd.edu/~ababakha/ >>>> >>>> >>>> >>>>  >>>> SF.Net email is sponsored by: >>>> Check out the new SourceForge.net Marketplace. >>>> It's the best place to buy or sell services for >>>> just about anything Open Source. >>>> http://sourceforge.net/services/buy/index.php >>>> _______________________________________________ >>>> apbsusers mailing list >>>> apbsusers@... >>>> https://lists.sourceforge.net/lists/listinfo/apbsusers >>>> >>> >>> >>> >>>  >>> Associate Professor, Dept. of Biochemistry and Molecular Biophysics >>> Center for Computational Biology, Washington University in St. Louis >>> Web: http://cholla.wustl.edu/ >>> >> >> >>  >> Arneh Babakhani >> McCammon Lab >> Department of Chemistry & Biochemistry >> University of California at San Diego >> 9500 Gilmand Dr MC 0365 >> La Jolla, CA 920930365 >> (619)8956540 >> (858)5344974 (FAX) >> ababakha@... >> http://mccammon.ucsd.edu/~ababakha/ >> >> >>  >> SF.Net email is sponsored by: >> Check out the new SourceForge.net Marketplace. >> It's the best place to buy or sell services for >> just about anything Open Source. >> http://sourceforge.net/services/buy/index.php >> _______________________________________________ >> apbsusers mailing list >> apbsusers@... >> https://lists.sourceforge.net/lists/listinfo/apbsusers > >  > Associate Professor, Dept. of Biochemistry and Molecular Biophysics > Center for Computational Biology, Washington University in St. Louis > Web: http://cholla.wustl.edu/ > > >  Arneh Babakhani McCammon Lab Department of Chemistry & Biochemistry University of California at San Diego 9500 Gilmand Dr MC 0365 La Jolla, CA 920930365 (619)8956540 (858)5344974 (FAX) ababakha@... http://mccammon.ucsd.edu/~ababakha/ 
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