Possible involvement of collective domain movement in the catalytic reaction of soluble epoxide hydrolase

Abstract

AbstractThe hydrolysis of 1S,2S‐trans‐methylstyrene oxide by soluble epoxide hydrolases is studied by a 4‐ns molecular dynamics (MD) simulation. An analysis of the extent of correlated motions in the active site was carried out. Based on the calculated cross correlation coefficients form the covariance matrix, a new correlation parameter, termed the supercorrelation coefficient, is introduced. The supercorrelation coefficient indicates the extent to which two amino acid residues move in a correlated manner with respect to all other residues in the protein. The resulting map of the supercorrelation coefficients was used to identify segments of the protein that may show collective domain movements. Interestingly, an anti‐correlated motion is located across the active site, involving the catalytic triad and the tyrosines. This may suggest that if a link exists between enzyme dynamics and catalysis, it may be through an anti‐correlated collective domain movement that compresses the active site, thus initiating the conversion of E–NAC to E–TS. © 2004 Wiley Periodicals, Inc. Int J Quantum Chem, 2004