AMBER Archive (2002)

Subject: dG of wild type/mutant

From: FyD (fyd_at_u-picardie.fr)
Date: Thu Mar 07 2002 - 05:26:31 CST

Dear All,

I would like to calculate the "dG" (free energy value) between a wild type
protein and one of its mutant (simple residue substitution, let's say for
instance: Ala45Pro). AMBER can estimate such values as a sum of the MM
energy, non-polar and electrostatic solvation (entropy might or might not be
computed). If I well understood, the mutant is constructed from the wild
type fold. My feeling is that using this wild type fold to construct the
mutant might be wrong in particular if the experimental mutant fold is
highly different from the wild type one. However, if the experimental mutant
fold is unknown, it is (for me) the unique solution. To get this dG value,
comparative molecular dynamics or minimization strategies are used. It is
clear that running two different dynamics on the wild type and mutant
proteins will provide better information on the dG value in particular (for
me) when the mutant fold is different from the wild type one.

Now if we apply the 'simple' minimization strategy on both proteins, is it
wrong to say that the dG value obtained show 'how much' the mutation is
unfavorable in the wild type fold (when the mutant fold is different from
the wild type one) or do we have to run molecular dynamics in this case (the
simulation time is not the same !) ?

Thanks, Sincerely,
Francois