[gmx-developers] Enthalpy decomposition and solvent-solvent interaction energies (extracted from g_energy)

[Tânia Firmino Guerra Guerreiro Cova]

Dear All, 

I'm trying to decompose the enthalpic profile of a set
of noncovalent complexes, containing beta-cyclodextrin and small drugs,
substituted with hydrophobic, hydrophilic and charged groups.
The
enthalpy change equals the potential energy difference with respect to
the unbonded state between host and guest.
The enthalpic profile of each
system can be further decomposed into eight terms, 

DeltaH =
DeltaH_host + DeltaH_guest + DeltaH_hostguest + DeltaH_hostsol+
DeltaH_guestsol + DeltaH_hosthost + DeltaH_guestguest + DeltaH_solsol


where the first two terms contain bonded interactions and the
remaining terms are inter- and intramolecular nonbonded interactions.


My question is related to the correct procedure for the simulation of
the completely separate state between host and guest, and the correct
calculation of the solvent-solvent interaction term (DeltaH_solsol). 
In
a first approach, it was performed a simulation in which the atoms of
host and guest were restrained at a fixed reference position (completely
separated) in the same simulation box. As expected, there was a large
energy penalty for applying position restraints, and the solvent-solvent
interaction term was positive. It should be expected that the latter
term becomes negative, upon complexation.
In a second approach, two
different simulations corresponding to the solvation of each single
molecule (simulation 1 - host + solvent, simulation 2 - guest + solvent)
were performed. The number of water molecules was the same in both
simulations. From these simulations, the energies of interaction related
to host-host, host-solvent (from simulation 1), guest-guest and
guest-solvent (from simulation 2) were extracted. These include LJ-SR,
Coul-SR and the decomposed terms of the reciprocal sum for electrostatic
calculations using PME. However, two solvent-solvent contributions
(LJ-SR_SOL-SOL, Coul.SR_ SOL-SOL) can also be extracted from each
simulation. Can these terms simply be added? It seems to me
unreasonable, given the doubling of water molecules ...
What is the
correct procedure for the simulation used as reference and corresponding
to the completely separate state between host and guest?

I have used a
similar procedure reported in J. Chem. Theory Comput., 2013, 9 (10), pp
4542-4551 (DOI: 10.1021/ct400404q), but it is not clear to me what to do
in the separate state. 

Can you please help me to understand which
procedure or kind of corrections should I use? 

Thank you in advance
for every kind of help. 

Firmino 
 



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