Re: [AMBER] Electrostatic energy calculated by MD in MM/GBSA

From: menwer momo <>
Date: Fri, 18 Jul 2014 13:38:42 -0700

Thank you for your reply.
Yes I am testing protein mutants on the same DNA, and the "free DNA" contribution are
identical for every mutant system. 
I am know trying to explain how each mutant affected the binding free energy,
For example when I mutated Thr to Ala the electrostatic energy as calculated by MD became more negative, which is opposite of what I expected, so should I interpret this change by saying that this mutation caused the favorable electrostatic energy to increase ?

Thanks again.

On Friday, July 18, 2014 11:19 PM, Jason Swails <> wrote:

On Fri, Jul 18, 2014 at 1:06 PM, menwer momo <> wrote:

> Dear Amber users,
>  If a mutation caused the electrostatic energy as calculated by molecualr
> dynamics to become more negative can I say that it increased the favorable
> electrostatic interactions?

​Barring error and uncertainty in your calculation, I would say that the
mutation was stabilizing.  You can look at the energy components to try and
assign this stabilization to electrostatic (EEL), polar solvation (EGB),
nonpolar solvation (ESURF/ENPOLAR), or dispersion (vdW) effects.


> ​​
> Note: I calculated the binding free energy for protein-DNA complex in
> addition to several  point mutants-DNA complexes  using MM/GBSA and  I want
> to
> ​​
> explain the change that occured due to the mutations on the electrostatic
> energy as calculated by MD.

​I've had conversations with people (or a person) that detailed some
difficulties in using the traditional single-trajectory approach of MM/GBSA
or MM/PBSA calculations on a set of mutants.  According to the
thermodynamic cycle of MM/PBSA (see​, if you are testing
protein mutants on the same DNA, then the "free DNA" contribution should be
identical for every mutant system.  If this is not true, then you have
introduced systematic error into your calculation that could skew your
results that you can only correct by using a multiple trajectory approach.

The good thing is that you can check for this just by comparing the DNA
contribution to binding in all of the output files.

Hope this helps,

Jason M. Swails
Rutgers University
Postdoctoral Researcher
AMBER mailing list
AMBER mailing list
Received on Fri Jul 18 2014 - 14:00:02 PDT
Custom Search