Differences of Atomic-Level Interactions between Midazolam and Two CYP Isoforms 3A4 and 3A5.

ABSTRACT: CYP 3A4 and CYP 3A5 are two important members of the human cytochrome P450 family. Although their overall structures are similar, the local structures of the active site are different, which directly leads to obvious individual differences in drug metabolic efficacy and toxicity. In this work, midazolam (MDZ) was selected as the probe substrate, and its interaction with two proteins, CYP 3A4 and CYP 3A5, was studied by molecular dynamics simulation (MD) along with the calculation of the binding free energy. The results show that two protein-substrate complexes have some similarities in enzyme-substrate binding; that is, in both complexes, Ser119 forms a high occupancy hydrogen bond with MDZ, which plays a key role in the stability of the interaction between MDZ and the enzymes. However, th

SUBMITTER: Liu S 

PROVIDER: S-EPMC10574787 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature