Re: [AMBER] Enthalpy of solute+solvent

From: Sergey Samsonov <>
Date: Tue, 19 Jan 2016 09:42:39 +0100

Sorry for my questions being redundant. I just saw this tutorial, which
completely addresses what I formulated in my previous e-mail:



On 01/18/2016 04:12 PM, Sergey Samsonov wrote:
> Dear Ambers,
> I wonder if there is a possibility in AMBER at the moment to calculate
> the enthalpic effect of explicit solvent to binding. Recently I
> encountered this paper:
> where, if I correctly understand the authors, they extracted internal
> energy corresponding to solute-solute, solute-solvent and
> solvent-solvent interactions from the trajectory using H=E+pV and
> ignoring pV contribution as negligible. They used CHARMM. I wonder,
> would it make sense to do something like this in AMBER:
> - to extract solute-solute interactions from the trajectory of the
> complex using LIE or simply in vacuo ELE+VDW from MM-PBSA/MM-GBSA;
> - for three long enough separate trajectories of complex, receptor and
> ligand in explicit solvent to define always the same amount of the water
> molecules around the solutes and extract the corresponding trajectories
> using 'closest' command, and then to use min=5 to estimate all ELE and
> VDW contributions corresponding to non-bonded interactions in the system
> (solvate-solvent and solvent-solvent).
> Because the number of water molecules for each system (complex,
> receptor, ligand) will be the same, the obtained numbers should be
> comparable though there are some problems I would expect:
> - if there are too many water molecules taken into account with the
> 'closest' approach, the results will be very noisy;
> - if there are not enough water molecules taken into account the
> differences in shape/geometry of the receptor and ligand could be
> crucial for the energies obtained like this because the hydration shells
> around a global protein and, for example, an elongated peptidic ligand,
> have very different shapes of the volumes and, therefore, amounts of
> interactions.
> What is your opinion: can this kind of approach yield anything valuable
> or it should be expected to be extremely noisy/unreliable anyway?
> As an alternative I see MM-PBSA/MM-GBSA approaches to calculate the
> enthalpy, which can be combined with umbrella sampling/SMD free energy
> calculations for the full free energy G in explicit solvent. In this
> case, the solvent is taken into account explicitly for G but implicitly
> for H. Depending on the GBSA-model the difference G-H and, therefore,
> the entropy can differ a lot quantitatively. However, if this is applied
> for very similar systems, do you think a certain qualitative pattern of
> the contributions of S and H components to G can be discussed at all
> also in terms of solvent impact?
> I found many discussions on the Mailing List from several years ago
> touching this topic. However, for me it is still not clear if some
> calculations taken into account solvent can be feasible or not at the
> moment.
> Thank you very much in advance for sharing your opinion.
> Cheers,
> Sergey

Sergey A. Samsonov
Postdoctoral researcher
Structural Bioinformatics
Biotechnology Center
Tatzberg 47-51
01307 Dresden, Germany
Tel: (+49) 351 463 400 83
Fax:   (+49) 351 463 402 87
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Received on Tue Jan 19 2016 - 01:00:04 PST
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