Hi Javier –

 

If you are trying to compare mutants, then I would recommend calculating

 

                \Delta \Delta G = \Delta G(binding, mutant) - \Delta G(binding, wild type)

 

That should be a more informative quantity.

 

Thanks,

 

--

Nathan Baker

Laboratory Fellow

Pacific Northwest National Laboratory

+1-509-375-3997

http://www.linkedin.com/in/nathanandrewbaker/

 

From: Javier Cáceres [mailto:jav.cdp@gmail.com]
Sent: Monday, September 02, 2013 9:50 AM
To: apbs-users@googlegroups.com
Cc: Javier Cáceres; APBS-USERS mailing list (apbs-users@lists.sourceforge.net); Baker, Nathan
Subject: Re: [apbs-users] Problem with getting positive binding energies

 

Hi Nathan,

Im trying to make electrostatic binding energies calculation of a wild-type complex and compare this with a lot of mutants, specifically mutating residues that are in the interface.

I follow this tutorial  https://sites.google.com/site/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 - receptor, and also I got positive energies. I use pdb2pqr to do my 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 what Im doing wrong, and what is the best accurate method for my calculation, the one form the tutorial, the (complex - ligand - receptor), the (comple - comple_ref - ligand + ligand_ref - receptor + receptor_ref), 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,

Javier.

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

Hello –

 

It would be useful to know more about your calculation.  However, it is important to recognize that APBS only calculates 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 contribute important entropic and enthalpic terms to the energy which are not calculated by APBS.

 

Implicit solvent calculation methods such as APBS are often most useful in calculating relative free energy differences (e.g., changes upon mutation) if you are willing to assume that some of the free energy components don’t change very much from mutant to mutant.

 

I hope this helps,

 

--

Nathan Baker

Laboratory Fellow

Pacific Northwest National Laboratory

+1-509-375-3997

http://www.linkedin.com/in/nathanandrewbaker/

 

From: Javier Cáceres [mailto:jav...@gmail.com]
Sent: Friday, August 30, 2013 9:58 AM
To: apbs-...@googlegroups.com
Subject: [apbs-users] Problem with getting positive binding energies

 

Hello APBS users,

Im trying to calculate binding energies for a protein-protein complex. Until now, my calc only gave me positive values, which is contradictory because that means that energy desetabilizes the
complex formation. I read and some papers say that the dielectric boundaries 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 case you want to see.
Thanks and I'll wait for you help.

Javier.