Investigating the structure and gating of membrane proteins via simulation of mixed-resolution models

COLL 403

Sven Jakobtorweihen, Edward Lyman, Lanyuan Lu, and Gregory A. Voth, voth@chem.utah.edu. Center for Biophysical Modeling & Simulation, University of Utah, 315 S. 1400 E, RM 2020, Salt Lake City, UT 84112-0850
Molecular simulation has become a standard tool to study membrane proteins, which are physiologically very important. A major limitation of classical molecular simulations is the time and lengths scales accessible; commonly time scales of the order of nanoseconds are reachable, whereas, the time scales in biological process are often orders of magnitude longer. A very promising method to increase the accessible time and length scales is coarse-grained modeling. These models reduce the number of interaction sites, at the expense of losing some molecular details of the system. To balance the need for atomistic detail against the performance of coarse-grained models, we have developed mixed-resolution models of membrane proteins. In these models the interesting region of the system is in atomic detail (here the protein) and the rest of the system (here water and lipids) are coarse-grained. In this work we introduce a new systematic way to build such mixed-resolution models using the multiscale coarse-graining method. Mixed-resolution simulation results of two important membrane proteins are presented: The mechanosensitive channel of large conductance (MscL), and bovine rhodopsin. Structural properties and gating mechanisms are studied.