[gmx-users] How to calculate the free energy difference of solvation for a Tyr-Phe mutation!

[Mikko Hellgren]

Hi all, 
I would like to get some advice on how to calculate the free energy difference of solvation between two proteins, a native (about 700AA) and one with a single mutation of a Tyr to Phe. 
The Tyr residue is located in the exterior of the protein structure and involved in two hydrogen bonds from the hydroxyl group to two other residues in the protein. From CD spectra we know that the spectra is unchanged by this mutation and this indicate a conserved secondary structure. The structure of the native protein is known but not for the mutant - can one from these background data get support that there is only minor changes in the structure between the native and the mutant and that these changes could be modeled well with a "long" MD simulation?
Could the Linear response theory be used for calculation of the free energy difference of solvation for the single mutation or do I have to do something a bit more fancy? Or could one perhaps use experimental data for solvation free energy differences between amino acids?....Anyhow I would like to get a suggestion on how this can be calculated.
I would also be great-full for any suggestions of a suitable MD tutorial or review article on the subject. 
Thanks for any advice or comments on these not so specific questions - sry about that!

Mikko Hellgren - Graduate Student
mikko.hellgren at ki.se 


____________________________________________________ 
One cannot avoid making mistakes if one tries to produce a set of words, or of mathematical formulae, to describe nature. Nature is more complicated than language or mathematics. Nevertheless, one must do one's best to produce a set of symbols which are not to discordant with the facts. 
J.B.S. Haldane, preface to "What is Life?", Lindsay Drummond, 1949
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