Dear sir,
I performed alanine scanning mutagenesis for several spot residues at a protein-ligand interface with MM-GBSA method. I run a md for the wildtype first, then mutated one residue at a time by truncating it at Cγon the same set of snapshots and recomputed the binding free energy.when comparing calculated ∆∆Gbinding with the corresponding experimental values, the alanine mutation of charged residues (asp, arg, gln) generated ∆∆Gbinding(4~6 kcal/mol) in significantly disagreement with experimental ones (1~2 kcal/mol). I analysed contribution of Ele, vdW, polar and nonplar solvation contribution to ∆∆Gbinding and found that the change in electrostatic energy upon deleting charged groups was mainly responsible for the deviation. Thus, I was wondering whether MM-GBSA was sensible with ele and failed to make accurate prediction on alanine scanning.
thank you
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Received on Tue Jun 21 2011 - 18:00:03 PDT
