Re: [Apbs-users] Binding energies in apbs
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Re: [Apbs-users] Binding energies in apbs
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From: Nathan B. <ba...@cc...> - 2008-01-07 14:33:04
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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/ |