AMBER Archive (2003)

Subject: Re: 2 questions

From: David A. Case (case_at_scripps.edu)
Date: Fri May 09 2003 - 10:54:41 CDT

On Fri, May 09, 2003, FyD wrote:
>
> - If we take the AMBER FF equation, is the hydrophobic interaction between 2
> aromatic residues (for instance) taken into account ? Is it through the vdW
> term ?

The hydrophobic effect is an indirect effect arising from solvation. There
is no specific term in the force field that represents it (for explict
solvent); rather, it arises "naturally" from the nature of the interactions.

>
> - Starting from a wild type fold, I mutated a residue. Using the GBSA
> strategy, I get a dE(effective) value of 8 kcal/mol and a dG value of 13
> kcal/mol between the mutant and the wild type protein (1 nanosec productive
> MD with GB). Can I conclude that the mutation present a stabilisation or a
> de-stabilisation effect ? To my opinion, such a dG is too small...
>

Are you using a real thermodynamic cycle: perform the mutation in the protein,
then again in small model system (e.g. a single amino acid), then compute
delta-delta-G by difference of the above two numbers. A single mutation
delta-G value has no meaning, just differences. And, as others have said,
13 kcal is actually pretty big.

..good luck..dac 

-- 

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