Thermodynamics of camphor migration in cytochrome P450cam by atomistic simulations.

ABSTRACT: Understanding the mechanisms of ligand binding to enzymes is of paramount importance for the design of new drugs. Here, we report on the use of a novel biased molecular dynamics (MD) methodology to study the mechanism of camphor binding to cytochrome P450cam. Microsecond-long MD simulations allowed us to observe reaction coordinates characterizing ligand diffusion from the active site of cytochrome P450cam to solvent via three egress routes. These atomistic simulations were used to estimate thermodynamic quantities along the reaction coordinates and indicate diverse binding configurations. The results suggest that the diffusion of camphor along the pathway near the substrate recognition site (SRS) is thermodynamically preferred. In addition, we show that the diffusion near the SRS is trigg

SUBMITTER: Rydzewski J 

PROVIDER: S-EPMC5552751 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature