Binding Energies for a Peptide-RNA System

From: rossi_at_york.cuny.edu
Date: Sat Sep 17 2005 - 14:37:11 CDT

Dear All:

I am all over the place on this question and am writing for help and guidance.

First let me say that I like the NAMD2.6b1 sections on Free Energy Perturbation
calculations as well as the tutorial by Dixit, Henin, and Chipot.

But, here are my questions:

1) NAMD uses Free Energy Perturbation to obtain energies for alchemical
transformations which can provide information on the relative binding
affinities of two separate ligands.

But what is the Themodynamic Integration Method? Try doing a Google search or
looking at some of this type of liturature to obtain a clear distinction
between FEP and Thermodynamic Integration. Forget it! From my point of view
these methods are very similar.

Can someone help out with a good explanation of how these two methods differ?

2) Gosh, I'd like to get an absolute binding free energy for a peptide-rna
system (so would a lot of people, I suspect).

Why don't researchers use FEP calculations to gradually allow the ligand to
disappear from the rna pocket in water and out of water to obtain an absolute
binding energy. That is, one would use the usual thermodynamic cycle to obtain
the differential binding energy between the two ligands, but one ligand is
null.

I really haven't seen this in the liturature.

Is the reason that the "perturbation" is too drastic in the sense that the
perturbation should be very local and modify the ligan slightly.

Any insight into you are willing to provide will be very much appreciated.

Kind regards,

Angelo

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