(284a) Studying Conformational Changes of Mhp1 Using Unbiased All-Atom Molecular Simulation

atom Molecular Simulations

Pouyan Khakbaz and Jeffery Klauda

Department of Chemical and Biomolecular Engineering,

University of Maryland College Park, MD 20742

Abstract

Mhp1 is a secondary active transporter from nucleobase/cation symporter-1 (NCS1) family. We have developed the implicit-explicit membrane (IM-EX) hybrid simulation method to study conformational changes in secondary active transporters (1). This novel approach starts with IM simulations and certain conformations from the implicit simulations are placed in an explicit environment to obtain the final conformation. Studying conformational changes of Mhp1 is an important test to our IM-EX method. Three different conformations of Mhp1 are known, i.e., inward-open, outward-occluded and outward-open (2). The implicit simulation was applied by using the SGLD method (3). The main advantage of the SGLD method is to overcome the energy barrier in a reasonable amount of simulation time. Crystal structures of different conformation were used as initial conformations for the SGLD simulations. Regular molecular dynamics and SGLD method was used for explicit membrane simulations to determine the efficiency of SGLD in explicit membrane environment. Separate sets of MD simulations starting with crystal structures were carried out as “control simulations” to test the effectiveness of our hybrid simulation method.

References:

1. Pendse & Klauda. JMB, 2010, 404:506

2. Shimamura & Weyand, Science, 2010, 328, 470-473

3. Wu & Brooks, J. Chem. Phys. , 2011, 135, 204101