Re: [Apbs-users] pH dependent binding energy and individual saltbridgecalculations
Biomolecular electrostatics software
Brought to you by:
sobolevnrm
Menu
▾
▴
Re: [Apbs-users] pH dependent binding energy and individual saltbridgecalculations
|
From: Jayita G. <ja...@ca...> - 2008-08-11 14:28:53
|
Hi Nathan, I used the pdq2pqr server to get pqr files for each domain and full-length using PROPKA to assign protonation states at each pH. Then I read the pqr files (2 domains and FL) in PMV and used the APBS plugin binding energy calculator that ran the program with the following input file (pasting the input file for pqr's calculated at pH 4.5 as an example). Please advise on how to edit the input file to account for the energy associated with protonations in the total binding energy calculations. Thanks so much for your help. Jayita. _______ APBS Input file for binding energy calculation: READ mol pqr dom2_pH4_5.pqr mol pqr dom1_pH4_5.pqr mol pqr FL_pH4_5.pqr END ELEC mg-auto mol 1 lpbe bcfl sdh chgm spl2 srfm spl2 swin 0.300 calcenergy total calcforce no write pot dx catdom_pH4_5.potential dime 65 65 65 cglen 99.739 94.181 89.680 cgcent 62.756 12.650 11.232 fglen 69.826 66.121 63.120 fgcent 62.756 12.650 11.232 gamma 0.105 temp 298.150 srad 1.400 sdie 78.540 pdie 2.000 ion 1.000, 0.150, 2.000 ion -1.000, 0.150, 2.000 END ELEC mg-auto mol 2 lpbe bcfl sdh chgm spl2 srfm spl2 swin 0.300 calcenergy total calcforce no write pot dx prodom_pH4_5.potential dime 65 65 65 cglen 99.739 94.181 89.680 cgcent 62.756 12.650 11.232 fglen 69.826 66.121 63.120 fgcent 62.756 12.650 11.232 gamma 0.105 temp 298.150 srad 1.400 sdie 78.540 pdie 2.000 ion 1.000, 0.150, 2.000 ion -1.000, 0.150, 2.000 END ELEC mg-auto mol 3 lpbe bcfl sdh chgm spl2 srfm spl2 swin 0.300 calcenergy total calcforce no write pot dx 2dom_pH4_5.potential dime 65 65 65 cglen 99.739 94.181 89.680 cgcent 62.756 12.650 11.232 fglen 69.826 66.121 63.120 fgcent 62.756 12.650 11.232 gamma 0.105 temp 298.150 srad 1.400 sdie 78.540 pdie 2.000 ion 1.000, 0.150, 2.000 ion -1.000, 0.150, 2.000 END PRINT energy 3 - 2 - 1 END QUIT ____________ > Hi Jayita -- > > To make sure I understand specifically how you're doing the > calculations: do you allow for different titration states between the > bound and unbound forms of the molecules? If so, do you account for > the energy associated with protonation in your "total" binding energy > that you'd like to compare with the Jensen paper? > > Thanks, > > Nathan > > On Aug 8, 2008, at 8:33 AM, Jayita Guhaniyogi wrote: > >> Thank you, Nathan for your suggestions and directing me to the >> previous >> works from Jensen and Alexov. >> One basic question, (I apologize for my ignorance)- what is the >> difference >> between the binding energy reported by APBS (calculated from >> subtracting >> the total electrostatic energies of the free domains/proteins from >> that of >> the complex) and the binding free energy (DeltaGb) that Mason and >> Jensen >> describe in the 2008 Proteins paper (Proteins 2008 71:81-91). >> Plots of binding energies Vs pH calculated from the above two methods >> (APBS and the DeltaG equation) have very different profiles, the >> latter >> being inverted bell-shaped while the former showing a negative energy >> plateau at higher pH without a negative energy peak. This seems to be >> conceptual. What am I missing? >> Thank you >> >> Jayita. >> >> >>> Hello -- >>> >>>> I am interested in analyzing the pH affect on binding energy between >>>> two >>>> domains in my protein of interest. I am working with a crystal >>>> structure >>>> of the full length form crystallized at pH 5.0. I used PROPKA to >>>> assign >>>> different protonation states to pqr files using the PDQ2PQR >>>> server at >>>> different pH's (pH 2.5 - pH 8.0). I generated pqr files for the >>>> full-length (complex) as well as for each of the 2 domains >>>> separately. I >>>> used the APBS plugin in Python Molecular Viewer to calculate >>>> individual >>>> and total electrostatic energies for each domain and full-length >>>> protein >>>> as well as binding energies between the two domains at each pH. The >>>> binding energy Vs pH profile reveals a trend and shows more positive >>>> binding energy at lower pH indicating destabilization of the >>>> interface. >>> >>> This sounds like a classic linked equilibrium analysis done with >>> implicit solvent models ala recent work from the Jensen group, Emil >>> Alexov and others... >>> >>>> I have two questions: >>>> 1) Is this a valid interpretation (realizing that this is only a >>>> prediction and I am assuming a static picture presented by the >>>> crystal >>>> structure at the different pHs, which is not going to be the case)? >>>> and, >>> >>> ...in short, I think it sounds like a very reasonable approach. >>> However, you should keep the caveats in mind: approximate titration >>> state/pKa assignment by PROPKA, implicit solvent limitations, static >>> structures, etc. >>> >>>> 2) Is it possible to look at the binding energies of individual salt >>>> bridge interactions between a given pair of acidic and basic >>>> residues at >>>> the interface and make similar interpretations about their stability >>>> at a >>>> given pH? If so, how? The apbs output file lists individual atomic >>>> energies during the calculation of electrostatic energies. Can I use >>>> these >>>> to calculate binding energies of individual salt bridges? If so, >>>> how? I am >>>> guessing these aren't simply additive. >>> >>> There's a couple of ways to do this; however, the most robust would >>> be >>> to neutralize the participating salt bridge residues and examine the >>> effect on the binding free energy. You could construct a free energy >>> cycle that involves charging/uncharging these residues to determine >>> the overall impact on the binding energy. >>> >>> Sounds like a fun project! >>> >>> -- Nathan >>> >>> >>>> >>>> Your help will be greatly appreciated. >>>> >>>> Jayita. >>>> >>>> >>>> -- >>>> Jayita Guhaniyogi, Ph.D. >>>> Postdoctoral Fellow >>>> Center for Advanced Biotechnology and Medicine >>>> Biochemistry, UMDNJ-RWJMS, >>>> Piscataway, NJ 08854 >>>> >>>> >>>> ------------------------------------------------------------------------- >>>> This SF.Net email is sponsored by the Moblin Your Move Developer's >>>> challenge >>>> Build the coolest Linux based applications with Moblin SDK & win >>>> great prizes >>>> Grand prize is a trip for two to an Open Source event anywhere in >>>> the world >>>> http://moblin-contest.org/redirect.php?banner_id=100&url=/ >>>> _______________________________________________ >>>> apbs-users mailing list >>>> apb...@li... >>>> https://lists.sourceforge.net/lists/listinfo/apbs-users >>> >>> -- >>> Associate Professor, Dept. of Biochemistry and Molecular Biophysics >>> Center for Computational Biology, Washington University in St. Louis >>> Web: http://cholla.wustl.edu/ >>> >>> >>> >>> >>> >>> >> >> >> -- >> Jayita Guhaniyogi, Ph.D. >> Postdoctoral Fellow >> Dr. Ann M. Stock's Laboratory >> Center for Advanced Biotechnology and Medicine >> Biochemistry, UMDNJ-RWJMS, >> Rm. 324 >> 679 Hoes Lane >> Piscataway, NJ 08854 >> 732-235-4206 >> >> ------------------------------------------------------------------------- >> This SF.Net email is sponsored by the Moblin Your Move Developer's >> challenge >> Build the coolest Linux based applications with Moblin SDK & win >> great prizes >> Grand prize is a trip for two to an Open Source event anywhere in >> the world >> http://moblin-contest.org/redirect.php?banner_id=100&url=/ >> _______________________________________________ >> apbs-users mailing list >> apb...@li... >> https://lists.sourceforge.net/lists/listinfo/apbs-users > > -- > Associate Professor, Dept. of Biochemistry and Molecular Biophysics > Center for Computational Biology, Washington University in St. Louis > Web: http://cholla.wustl.edu/ > > > > > > -- Jayita Guhaniyogi, Ph.D. Postdoctoral Fellow Dr. Ann M. Stock's Laboratory Center for Advanced Biotechnology and Medicine Biochemistry, UMDNJ-RWJMS, Rm. 324 679 Hoes Lane Piscataway, NJ 08854 732-235-4206 |