Abstract

Theoretical methods for correlation of sequence changes and redox potential of electron transport proteins are examined using the Asn52----Ile mutation in cytochrome c as a test case. The first approach uses the protein dipoles Langevin dipoles (PDLD) method and the high resolution X-ray structures of the native and the mutant proteins. This approach is found to give reliable results where all the solvent molecules are represented by Langevin dipoles and also when some bound water molecules are represented explicitly. A free energy perturbation method is also found to give reasonable results but at the expense of much more computer time. Finally, an approach that generates mutant structures from the native structure by molecular dynamics simulation and then uses these configurations in PDLD calculations is found to give a reasonable estimate of the effect of the mutation on the corresponding redox potential. The encouraging results obtained here and in a preliminary test case of the Phe82----Ser mutation indicates that the present strategies can provide a useful tool for structure-redox and sequence-redox correlation in proteins.