Molecular Dynamics Simulations of Large Integral Membrane Proteins with an Implicit Membrane Model

The heterogeneous dielectric generalized Born {(HDGB)} methodology is an the extension of the {GBMV} model for the simulation of integral membrane proteins with an implicit membrane environment. Three large integral membrane proteins, the bacteriorhodopsin monomer and trimer and the {BtuCD} protein, were simulated with the {HDGB} model in order to evaluate how well thermodynamic and dynamic properties are reproduced. Effects of the truncation of electrostatic interactions were examined. For all proteins, the {HDGB} model was able to generate stable trajectories that remained close to the starting experimental structures, in excellent agreement with explicit membrane simulations. Dynamic properties evaluated through a comparison of B-factors are also in good agreement with experiment and explicit membrane simulations. However, overall flexibility was slightly underestimated with the {HDGB} model unless a very large electrostatic cutoff is employed. Results with the {HDGB} model are further compared with equivalent simulations in implicit aqueous solvent, demonstrating that the membrane environment leads to more realistic simulations.