Free energy changes associated with amino acid substitution in proteins

Abstract
The estimation of free energy differences from computer simulation of macromolecular systems is important for rational strategies for drug design and for protein engineering. As an example of one mutation, we have studied the free energy change resulting from the conversion of a polar group (OH) to an apolar group (CH3) in aqueous solution. We have estimated the effect of various local environments on the magnitude of the free energy difference and find that significant environmental effects are found. We have also studied the reliability of the results in detail.