Parameterization of PACE Force Field for Membrane Environment and Simulation of Helical Peptides and Helix-Helix Association.

The recently developed PACE force field was further parametrized so that it can be applied to the studies of membrane systems. Parameters for the interactions between united-atom protein particles and lipid hydrophobic tails were developed by reproducing the solvation free energies of small organic molecules in hexadecane. Interactions between protein particles and lipid heads were parametrized by fitting the potential of mean force of the corresponding all-atom simulation. The force field was applied to the study of five helical peptides in membrane environments. The calculated tilt angles of WALP and GWALP and their mutations are in good agreement with experimental data. The association of two glycophorin A (GpA) helices was simulated for 6 μs. Root-mean-square-deviation of the simulated dimer from the nuclear magnetic resonance structure was found to be 0.272 nm, better than all results obtained so far. These findings demonstrate the high accuracy and applicability of the PACE force field in studying membrane proteins.