Re: [Apbs-users] Binding energies in apbs
Biomolecular electrostatics software
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From: Nathan B. <ba...@cc...> - 2008-01-09 14:25:36
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Hello -- This really only applies to the 'coulomb' program which calculates energies/forces analytically using Coulomb's law in a vacuum. If you use coulomb, then the results of this program (*not* the main APBS program) need to be scaled by whatever internal dielectric constant you're using in your polar solvation energy calculations with the main APBS program. -- Nathan On Jan 9, 2008 8:21 AM, Amit <am...@ho...> wrote: > > Dear Nathan, > Does the total electrostatic energy output also has to be scaled according > to the internal dielectric? I'm a little confused about the need for > scaling. Is this an APBS-related matter or a general one? When working with > similar tools before (e.g. DelPhi), I'd usually take the output as is. > Thanks, > Amit. > > > > > ________________________________ > > From: ba...@cc... > > To: aba...@mc... > > Date: Mon, 7 Jan 2008 08:33:03 -0600 > > CC: apb...@li... > > > > Subject: Re: [Apbs-users] Binding energies in apbs > > > > Hi Arneh -- > > > > > Regarding #2 in your comments below: Do the polar/apolar solvation > > > energies > > > have to be scaled as well? > > > > No; the only reason the Coulombic contributions are scaled is to > > account for a possibly non-vacuum reference state in the polar > > solvation calculations. > > > > > Remember our previous discussion of Autodock vs APBS calculated > > > solvation > > > energies? I was just looking at the numbers again, and I noticed > > > that for > > > one particular ligand, if I take the APBS calculated energy of > > > solvation > > > (49.4 kcal/mol) and divide that by the dielectric of water (78.4), I > > > get = > > > 0.6 kcal/mol. The AD calculated solvation energy is pretty close, = > > > 0.7 > > > kcal/mol. So by dividing the APBS result by the dielectric, I'm > > > able to > > > match up the two results more closely. Is this just a happy > > > coincidence??? > > > > I think that's a coincidence... sorry! :) > > > > -- Nathan > > > > > > > > Thanks, > > > > > > Arneh > > > > > > > > > -- > > > Arneh Babakhani > > > McCammon Lab > > > Department of Chemistry & Biochemistry > > > University of California at San Diego > > > 9500 Gilman Dr MC 0365 > > > La Jolla, CA 92093-0365 > > > (619)895-6540 > > > (858)534-4974 (FAX) > > > aba...@mc... > > > http://mccammon.ucsd.edu/~ababakha/ > > > -----Original Message----- > > > From: apb...@li... > > > [mailto:apb...@li...] On Behalf Of > > > Nathan Baker > > > Sent: Saturday, January 05, 2008 5:55 AM > > > To: Domenico Gatti > > > Cc: apb...@li... > > > Subject: Re: [Apbs-users] Binding energies in apbs > > > > > > Hello -- > > > > > > I'm sorry I haven't replied to your earlier e-mail yet; I've been > > > swamped with a grant deadline. > > > > > > These energies do seem too large and, without more knowledge of the > > > system, it's hard to say specifically why this might be. However, > > > here are a few of the common problems when binding energies are > > > calculated this way: > > > > > > (1) Grid is too coarse. Perhaps your grid resolution isn't fine > > > enough. This can be checked by running a subset of the calculations > > > at a finer grid spacing to see if the solvation energies change > > > significantly. > > > > > > (2) Coulombic energies weren't scaled properly. Did you divide your > > > Coulombic energies by the internal dielectric constant used for the > > > polar solvation energy calculations? > > > > > > (3) Parameter/surface mismatch. Which parameter sets and surface > > > definitions did you use? Along the same lines, what were your APOLAR > > > settings and radii used for those calculations? > > > > > > When the structures of A and B don't change upon complex formation, I > > > often prefer to calculate polar solvation energies directly through 3 > > > calculations: G(AB) - G(A) - G(B), where G(.) represents the total > > > electrostatic energy of a structure. When performing such > > > calculations, it's very important to ensure that A is exactly in the > > > same place on the grid as it is in AB when performing those two > > > calculations (same for B). The examples/actin-dimer test case gives > > > an example of this kind of calculation. > > > > > > Hope this helps, > > > > > > Nathan > > > > > > On Jan 4, 2008, at 11:20 PM, Domenico Gatti wrote: > > > > > >> Dear APBS Users, > > >> > > >> Being new to APBS I would really appreciate if you could tell me > > >> whether > > >> I am understanding correctly the meaning of the binding energies > > >> calculated > > >> by the various scripts. In equations 5.1, 5.2, and 5.3 of the > > >> tutorial the > > >> "Binding Free Energy" for a two component complex of molecules mol1 > > >> and mol2 > > >> is defined as an "association" binding free energy (-Delta3G of the > > >> cycle > > >> shown in Fig. 5.1), and therefore, > > >> > > >> DeltaG(bind)= -RTln(1/Kd) > > >> > > >> For example, I have used apbs to calculate the binding free energy > > >> for two > > >> monomers A and B forming the homodimer AB (from one of our X-ray > > >> structures). The following are the various components in kJ/mol with > > >> their > > >> signs as they appear in the log files: > > >> > > >> AB B A AB- > > >> B-A > > >> > > >> SOLV APOLAR 9866 4702 4710 454 > > >> > > >> SOLV POLAR -9540 -5254 -5000 714 > > >> > > >> COULOMBIC 362000 181000 180471 529 > > >> > > > > ____________________________________________________________________________ > > >> > > >> DeltaG(bind) 362326 180448 180181 > > >> 1697 > > >> > > >> > > >> 1697/-5.7 = -298 = log(1/Kd) > > >> > > >> Kd = 10^298 M > > >> > > >> > > >> > > >> This is not an isolated case in my hands. In another crystallographic > > >> complex (this time a dimeric protein (AB) that binds to a receptor > > >> C) I get > > >> the following results: > > >> > > >> ABC C AB ABC- > > >> C-AB > > >> > > >> SOLV APOLAR 15778 8115 7148 515 > > >> > > >> SOLV POLAR -17301 -10161 -7810 670 > > >> > > >> COULOMBIC 76928 40505 35794 629 > > >> > > > > ____________________________________________________________________________ > > >> > > >> DeltaG(bind) 75405 38459 35132 1814 > > >> > > >> > > >> 1814/-5.7 = -318 = log(1/Kd) > > >> > > >> Kd = 10^318 M > > >> > > >> > > >> Clearly, I must not be interpreting correctly the signs of the > > >> energies for > > >> the various components, or perhaps I am summing things that are not > > >> supposed > > >> to be summed. For example, if I calculate the COULOMBIC contribution > > >> by > > >> using a pqr file that contains all the molecules of the complex, but > > >> separated in space by over 40 angstroms, the energy goes down to > > >> almost > > >> nothing, suggesting that the COULOMBIC component represents a > > >> "dissociation" > > >> binding free energy. As such it should be subtracted from the > > >> solvation > > >> energy rather then added (as it is in the two tables above). In the > > >> second > > >> case that would give a binding free energy of 515+670-629=556 kJ/mol > > >> > > >> 556/-5.7 = -98 = log(1/Kd) > > >> > > >> Kd = 10^98 M > > >> > > >> > > >> On the other hand, if all my signs are wrong that would become > > >> > > >> Kd = 10^(-98) M > > >> > > >> which is equally hard to believe. > > >> > > >> I would be happy to send you my scripts, logs and pdb/pqr. > > >> > > >> Thanks again for your help and Happy New Year! > > >> > > >> Best, > > >> Domenico > > >> > > >> Domenico Gatti, MD PhD > > >> Assoc. Professor > > >> Biochemistry & Mol. Biology > > >> Wayne State University School of Medicine > > >> 540 E. Canfield Avenue > > >> Detroit, MI 48201 > > >> Tel: 313-577-0620 or 313-993-4238 > > >> Fax: 313-577-2765 > > >> dg...@me... > > >> > > >> > > >> > > >> > > >> > > >> > > >> > > >> > > >> > > >> > ------------------------------------------------------------------------- > > >> This SF.net email is sponsored by: Microsoft > > >> Defy all challenges. Microsoft(R) Visual Studio 2005. > > >> http://clk.atdmt.com/MRT/go/vse0120000070mrt/direct/01/ > > >> _______________________________________________ > > >> 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/ > > > > > > > > > > > > > > > > ------------------------------------------------------------------------- > > > This SF.net email is sponsored by: Microsoft > > > Defy all challenges. Microsoft(R) Visual Studio 2005. > > > http://clk.atdmt.com/MRT/go/vse0120000070mrt/direct/01/ > > > _______________________________________________ > > > apbs-users mailing list > > > apb...@li... > > > https://lists.sourceforge.net/lists/listinfo/apbs-users > > > > > > > > > > ------------------------------------------------------------------------- > > > This SF.net email is sponsored by: Microsoft > > > Defy all challenges. Microsoft(R) Visual Studio 2005. > > > http://clk.atdmt.com/MRT/go/vse0120000070mrt/direct/01/ > > > _______________________________________________ > > > 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/ > > > > > > > > > > ------------------------------------------------------------------------- > > This SF.net email is sponsored by: Microsoft > > Defy all challenges. Microsoft(R) Visual Studio 2005. > > http://clk.atdmt.com/MRT/go/vse0120000070mrt/direct/01/ > > _______________________________________________ > > apbs-users mailing list > > apb...@li... > > https://lists.sourceforge.net/lists/listinfo/apbs-users > > ________________________________ > Watch "Cause Effect," a show about real people making a real difference. > Learn more -- Associate Professor, Dept. of Biochemistry and Molecular Biophysics Center for Computational Biology, Washington University in St. Louis Web: http://cholla.wustl.edu/ |