Content-Type: multipart/alternative; boundary="----=_Part_2715_4200948.1378140605790" ------=_Part_2715_4200948.1378140605790 Content-Type: text/plain; charset=UTF-8 Content-Transfer-Encoding: quoted-printable Hi Nathan, Im trying to make electrostatic binding energies calculation of a wild-type= =20 complex and compare this with a lot of mutants, specifically mutating=20 residues that are in the interface.=20 I follow this tutorial =20 https://sites.google.com/site/wangtingpage/home/tutorials and the energies= =20 that I got are all positives, for the WT and for the mutants. I also did the calculation of energies with: complex - ligand - receptor,= =20 and also I got positive energies. I use pdb2pqr to do my files, and=20 followed the redomendation of grid and others that gave me.=20 Also, the problem is that all the mutants has similar energies. I don't=20 know what Im doing wrong, and what is the best accurate method for my=20 calculation, the one form the tutorial, the (complex - ligand - receptor),= =20 the (comple - comple_ref - ligand + ligand_ref - receptor + receptor_ref),= =20 using the coulomb program to do the calculation of de coulombic part, etc.. Sorry if Im a little lost, but Im trying to understand. Thanks Nathan,=20 Javier. On Monday, September 2, 2013 11:05:18 AM UTC-4, Baker, Nathan wrote: > > Hello =E2=80=93 > > =20 > > It would be useful to know more about your calculation. However, it is= =20 > important to recognize that APBS only calculates a portion of the overall= =20 > binding energy: the electrostatic (polar solvation) contribution and,=20 > depending on how you configure the calculation, the apolar solvation=20 > contribution. Conformational changes can contribute important entropic a= nd=20 > enthalpic terms to the energy which are not calculated by APBS. > > =20 > > Implicit solvent calculation methods such as APBS are often most useful i= n=20 > calculating relative free energy differences (e.g., changes upon mutation= )=20 > if you are willing to assume that some of the free energy components don= =E2=80=99t=20 > change very much from mutant to mutant. > > =20 > > I hope this helps, > > =20 > > -- > > Nathan Baker > > Laboratory Fellow > > Pacific Northwest National Laboratory > > +1-509-375-3997 > > http://www.linkedin.com/in/nathanandrewbaker/=20 > > =20 > > *From:* Javier C=C3=A1ceres [mailto:jav...@gmail.com ]=20 > *Sent:* Friday, August 30, 2013 9:58 AM > *To:* apbs-...@googlegroups.com > *Subject:* [apbs-users] Problem with getting positive binding energies > > =20 > > Hello APBS users, > > Im trying to calculate binding energies for a protein-protein complex.=20 > Until now, my calc only gave me positive values, which is contradictory= =20 > because that means that energy desetabilizes the > complex formation. I read and some papers say that the dielectric=20 > boundaries are important for de sign of the energy. I use srad values of= =20 > 0.00 and 1.4, but with this I only got changes in the magnitude but not i= n=20 > the sign. > I can't find what Im doing wrong. I attached the input file in case you= =20 > want to see. > Thanks and I'll wait for you help. > > Javier. > ------=_Part_2715_4200948.1378140605790 Content-Type: text/html; charset=utf-8 Content-Transfer-Encoding: quoted-printable
Hi Nathan,

Im trying to=20 make electrostatic binding energies calculation of a wild-type complex=20 and compare this with a lot of mutants, specifically mutating residues=20 that are in the interface.
I follow this tutorial  https://sites.google.com/si= te/wangtingpage/home/tutorials and the energies that I got are all= positives, for the WT and for the mutants.
I also did the calculation of energies with: complex - ligand -=20 receptor, and also I got positive energies. I use pdb2pqr to do my=20 files, and followed the redomendation of grid and others that gave me.
=
Also, the problem is that all the mutants has similar energies. I don't know=20 what Im doing wrong, and what is the best accurate method for my=20 calculation, the one form the tutorial, the (complex - ligand -=20 receptor), the (comple - comple_ref - ligand + ligand_ref - receptor +=20 receptor_ref), using the coulomb program to do the calculation of de=20 coulombic part, etc..
Sorry if Im a little lost, but Im trying to understand.
Than= ks Nathan,

Javier.

On Monday, September 2, 2013 11:05:= 18 AM UTC-4, Baker, Nathan wrote:

Hello =E2=80=93

= It would be useful to know more about your calcu= lation.  However, it is important to recognize that APBS only calculat= es a portion of the overall binding energy:  the electrostatic (polar = solvation) contribution and, depending on how you configure the calculation= , the apolar solvation contribution.  Conformational changes can contr= ibute important entropic and enthalpic terms to the energy which are not ca= lculated by APBS.

Impli= cit solvent calculation methods such as APBS are often most useful in calcu= lating relative free energy differences (e.g., changes upon mutation) if yo= u are willing to assume that some of the free energy components don=E2=80= =99t change very much from mutant to mutant.

I hope this helps,

<= span style=3D"font-size:11.0pt;font-family:"Calibri","sans-s= erif";color:#1f497d">

--

Nathan Baker

Laboratory Fellow

Pacific Northwest National Laboratory

+1-509-375-3997

&n= bsp;

From: Javier C=C3=A1ceres [mailto:jav...@gmail.com]
Sent:= Friday, August 30, 2013 9:58 AM
Subject: [apbs-users] Problem with getting positive b= inding energies

Hello APBS users,

Im trying to calculate binding energie= s for a protein-protein complex. Until now, my calc only gave me positive v= alues, which is contradictory because that means that energy desetabilizes = the
complex formation. I read and some papers say that the dielectric bo= undaries are important for de sign of the energy. I use srad values of 0.00= and 1.4, but with this I only got changes in the magnitude but not in the = sign.
I can't find what Im doing wrong. I attached the input file in cas= e you want to see.
Thanks and I'll wait for you help.

Javier.

=
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