Conformational Activation of a Transmembrane Proton Channel from Constant pH Molecular Dynamics.

ABSTRACT: Proton-coupled transmembrane proteins play important roles in human health and diseases; however, detailed mechanisms are often elusive. Experimentally resolving proton positions and structural details is challenging, and conventional molecular dynamics simulations are performed with preassigned and fixed protonation states. To address this challenge, here we illustrate the use of the state-of-the-art continuous constant pH molecular dynamics (CpHMD) to directly describe the activation of the M2 channel of influenza virus, for which abundant experimental data are available. Starting from the closed crystal structure, simulation reveals a pH-dependent conformational switch to an activated state that resembles the open crystal structure. Importantly, simulation affords the free energy of cha

SUBMITTER: Chen W 

PROVIDER: S-EPMC5718886 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature