Adaptive Accelerated Molecular Dynamics (Ad-AMD) Revealing the Molecular Plasticity of P450cam.

ABSTRACT: An extended accelerated molecular dynamics (AMD) methodology called adaptive AMD is presented. Adaptive AMD (Ad-AMD) is an efficient and robust conformational space sampling algorithm that is particularly-well suited to proteins with highly structured potential energy surfaces exhibiting complex, large-scale collective conformational transitions. Ad-AMD simulations of substrate-free P450cam reveal that this system exists in equilibrium between a fully and partially open conformational state. The mechanism for substrate binding depends on the size of the ligand. Larger ligands enter the P450cam binding pocket, and the resulting substrate-bound system is trapped in an open conformation via a population shift mechanism. Small ligands, which fully enter the binding pocket, cause an induced-fit

SUBMITTER: Markwick PR 

PROVIDER: S-EPMC3034398 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature