continuum molecular simulation of large conformational changes during ion–channel gating连续体构象变化在离子通道的分子模拟控制.pdfVIP

Continuum Molecular Simulation of Large Conformational Changes during Ion–Channel Gating Ali Nekouzadeh*, Yoram Rudy* Cardiac Bioelectricity and Arrhythmia Center and Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, Missouri, United States of America Abstract A modeling framework was developed to simulate large and gradual conformational changes within a macromolecule (protein) when its low amplitude high frequency vibrations are not concerned. Governing equations were derived as alternative to Langevin and Smoluchowski equations and used to simulate gating conformational changes of the Kv7.1 ion- channel over the time scale of its gating process (tens of milliseconds). The alternative equations predict the statistical properties of the motion trajectories with good accuracy and do not require the force field to be constant over the diffusion length, as assumed in Langevin equation. The open probability of the ion–channel was determined considering cooperativity of four subunits and solving their concerted transition to the open state analytically. The simulated open probabilities for a series of voltage clamp tests produced current traces that were similar to experimentally recorded currents. Citation: Nekouzadeh A, Rudy Y (2011) Continuum Molecular Simulation of Large Conformational Changes during Ion–Channel Gating. PLoS ONE 6(5): e20186. doi:10.1371/journal.pone.0020186 Editor: Raya Khanin, Memorial Sloan Kettering Cancer Center, United States of America Received September 15, 2010; Accepted April 27, 2011; Published May 20, 2011 Copyright: 2011 Nekouzadeh, Rudy. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distrib