Induced fit for cytochrome P450 3A4 based on molecular dynamics.

ABSTRACT: The present study aims at numerically describing to what extent substrate - enzyme complexes in solution may change over time as a natural process of conformational changes for a liganded enzyme in comparison to those movements which occur independently from substrate interaction, i.e. without a ligand. To this end, we selected structurally known pairs of liganded / unliganded CYP450 3A4 enzymes with different geometries hinting at induced fit events. We carried out molecular dynamics simulations (MD) comparing the trajectories in a "cross-over" protocol: (i) we added the ligand to the unliganded crystal form which should adopt geometries similar to the known geometry of the liganded crystal structure during MD, and - conversely - (ii) we removed the bound ligand form the known liganded co

SUBMITTER: Quiroga I 

PROVIDER: S-EPMC8963583 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature