[gmx-users] RE: Gibbs free energy of binding

[Sander Pronk]

To put some numbers to what David said, here's an experimental paper on a well-studied drug-protein complex:
http://pubs.acs.org/doi/pdf/10.1021/bi001013s

the entropic contribution of HIV-1 protease inhibitor binding is about 3x bigger than the enthalpic contribution for all 4 drugs studied there. 

I'm not sure if that's a special case, but if you're leaving out entropy you are at the very least doing an uncontrolled approximation - you don't know how big the term is you're missing, and it could be the dominant term.

Sander


On 21 Oct 2010, at 10:45 , David van der Spoel wrote:

> On 2010-10-21 10.39, Ehud Schreiber wrote:
>> Actually, I believe that using the energy difference, Delta E, as an
>> approximation to the free energy difference, Delta G, is a valid
>> approach (which I'm considering myself). The entropic contribution to
>> Delta G, namely -T Delta S, may be less prominent than Delta E.
>> In addition, Delta S can be approximated by various means - see e.g.
>> Doig&  Sternberg 1995. I understand that such an approach is utilized in
>> the Accelrys Discovery Studio.
>> Obviously, this is an approximation that might be too crude for some
>> applications.
> 
> As a simple example the hydrophobic effect at room temperature is largely due to the entropy of the water [ at high temp it is due to the enthalpy of the water ].
> 
> Since the hydrophobic effect is involved in all ligand binding it seems quite hopeless to get any reliable numbers when neglecting entropy. No referee will buy that - I wouldn't.
> 
>> 
>> What do you think?
>> 
>> ------------------------------------------------------------------------
>> --
>> 
>> On Oct 21, 2010, at 09:25 , Sander Pronk wrote:
>> 
>> Hi Mohsen,
>> 
>> The mean energy difference is only one component of the free energy
>> difference.
>> 
>> Before you go any further I'd suggest reading a good book on molecular
>> simulations, like 'Understanding Molecular Simulations' by Frenkel and
>> Smit.
>> 
>> There's a good reason free energy calculations cover over half of that
>> book.
>> 
>> Sander
>> 
>> 
>> On Oct 21, 2010, at 09:18 , mohsen ramezanpour wrote:
>> 
>>> Dear Justin
>>> 
>>> If I do  two  MD simulations for a short time in the same
>> conditions(of course separately for protein and drug)
>>>  and calculate total energy of each one and sum them with each other
>> as E1 as nonbonding free energy of system.
>>> then a MD simulation for Protein-drug system in the same condition and
>> calculate it's total energy too as E2 as bound system .
>>> what does (E1-E2)mean?
>>> I think it is binding free energy,Is not it?
>>> in the other hand when we are working on NPT ensamble it means Gibbs
>> free energy is the main energy and our total energy is equal to Gibbs
>> free energy.
>>> Then,what is the problem?
> 
> 
> -- 
> David van der Spoel, Ph.D., Professor of Biology
> Dept. of Cell & Molec. Biol., Uppsala University.
> Box 596, 75124 Uppsala, Sweden. Phone:	+46184714205.
> spoel at xray.bmc.uu.se    http://folding.bmc.uu.se
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