MOLECULAR-DYNAMICS STUDY OF TIME-CORRELATED PROTEIN DOMAIN MOTIONS AND MOLECULAR FLEXIBILITY - CYTOCHROME P450BM-3

Time-correlated atomic motions were used to characterize protein domai n boundaries from atomic coordinates generated by molecular dynamics s imulations, A novel application of the dynamical cross-correlation mat rix (DCCM) analysis tool was used to help identify putative protein do mains. In implementing this new approach, several DCCM maps were calcu lated, each using a different coordinate reference frame from which pr otein domain boundaries and protein domain residue constituents could be identified. Cytochrome P450BM-3, from Bacillus megaterium, was used as the model protein in this study. The analyses indicated that the s imulated protein comprises three distinct domain regions; in contrast, only two protein domains were identified in the original crystal stru cture report. Specifically, the DCCM analyses showed that the F-G heli x region was a separate domain entity and not a part of the a domain, as previously designated. The simulations demonstrated that the domain motions of the F-G helix region effected both the size and shape of t he enzyme active site, and that the dynamics of the F-G helix domain c ould possibly control access of substrate to the binding pocket.