title: Effect of the Asn52----Ile mutation on the redox potential of yeast cytochrome c. Theory and experiment.
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.
authors.affiliation: Department of Chemistry, University of Southern California, Los Angeles 90089-0482.
authors.forename: R
authors.initials: R
authors.lastname: Langen
authors.forename: G D
authors.initials: GD
authors.lastname: Brayer
authors.forename: A M
authors.initials: AM
authors.lastname: Berghuis
authors.forename: G
authors.initials: G
authors.lastname: McLendon
authors.forename: F
authors.initials: F
authors.lastname: Sherman
authors.forename: A
authors.initials: A
authors.lastname: Warshel
mesh_terms: D000595:Amino Acid Sequence; D001216:Asparagine / Q000235:genetics*; D003574:Cytochrome c Group / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D004563:Electrochemistry; D004579:Electron Transport; D007532:Isoleucine / Q000235:genetics*; D016296:Mutagenesis; D010084:Oxidation-Reduction; D011487:Protein Conformation; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D013329:Structure-Activity Relationship; D014867:Water / Q000737:chemistry
chemical_list: D003574:Cytochrome c Group; D007532:Isoleucine; D014867:Water; D001216:Asparagine