Water Exchange from the Buried Binding Sites of Cytochrome P450 Enzymes 1A2, 2D6, and 3A4 Correlates with Conformational Fluctuations.

ABSTRACT: Human cytochrome P450 enzymes (CYPs) are critical for the metabolism of small-molecule pharmaceuticals (drugs). As such, the prediction of drug metabolism by and drug inhibition of CYP activity is an important component of the drug discovery and design process. Relative to the availability of a wide range of experimental atomic-resolution CYP structures, the development of structure-based CYP activity models has been limited. To better characterize the role of CYP conformational fluctuations in CYP activity, we perform multiple microsecond-scale all-atom explicit-solvent molecular dynamics (MD) simulations on three CYP isoforms, 1A2, 2D6, and 3A4, which together account for the majority of CYP-mediated drug metabolism. The MD simulations employ a variety of positional restraints, ranging f

SUBMITTER: Guvench O 

PROVIDER: S-EPMC10820051 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature