[gmx-users] free energy calculation in a big system

[Anton Feenstra]

Markus O Kaukonen wrote:

> Dear All,
> 
> Never done any free energy calculation with a computer, so... :
> 
> Is it possible (cpu and otherwise) to do a free energy calculation for a
> system like in the manual (v 3.2 manual) page 36, fig. 3.9 case B
> ie. two different inhibitors (I and I') docking the same enzyme (E)
> when I and I' differ by one H+ (and the partial charges in I and I' are
> different).
> 
> I (one system) and I' (the other system) have about 200 atoms and
> E has 70000 atoms.
> 
> It seems at least that one has to do lot of things by hand in the topology
> file (for things related to those 200 atoms).

Yes. You'd need to build a topology & forcefield for I and I' (which will
be very similar, if I understand you).

A different problem is the size of I/I': 200 atoms. That probably means
there is quite a bit of (internal) flexibility in these molecules, which
may make it difficult to get enough conformational sampling for an accurate
(average) free energy difference to be calculated. In other words, you'll
need pretty long simulations. The upsinde is, you'd probably be able to do
free energy perturbation (FEP), seeing that 'only' charges and one H+ differ
between I and I'. This means, you'll need to simulate two complexes: the E-I
and the E-I', both fore several (tens of) nanoseconds, and then 'perturb'
the systems and look at the energy differences (IIRC, FEP is explained in
the manual).

So, bit of work but doable!

-- 
Groetjes,

Anton
  _____________ _______________________________________________________
|             |                                                       |
|  _   _  ___,| K. Anton Feenstra                                     |
| / \ / \'| | | Dept. of Pharmacochem. - Vrije Universiteit Amsterdam |
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| \_/ \_/ | | | Tel: +31 20 44 47608 - Fax: +31 20 44 47610           |
|             | Feenstra at chem.vu.nl - www.chem.vu.nl/~feenstra/       |
|             | "If You See Me Getting High, Knock Me Down"           |
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