A further parametrization of a united-atom protein model coupled with coarse-grained water has been carried out to cover all amino acids (AAs). The local conformational features of each AA have been fitted on the basis of restricted coil-library statistics of high-resolution X-ray crystal structures of proteins. Potential functions were developed on the basis of combined backbone and side chain rotamer conformational preferences, or rotamer Ramachandran plots (ϕ, Ψ, χ1). Side chain-side chain and side chain-backbone interaction potentials were parametrized to fit the potential mean forces of corresponding all-atom simulations. The force field has been applied in molecular dynamics simulations of several proteins of 56-108 AA residues whose X-ray crystal and/or NMR structures are available. Starting from the crystal structures, each protein was simulated for about 100 ns. The Cα RMSDs of the calculated structures are 2.4-4.2 Å with respect to the crystal and/or NMR structures, which are still larger than but close to those of all-atom simulations (1.1-3.6 Å). Starting from the PDB structure of malate synthase G of 723 AA residues, the wall-clock time of a 30 ns simulation is about three days on a 2.65 GHz dual-core CPU. The RMSD to the experimental structure is about 4.3 Å. These results implicate the applicability of the force field in the study of protein structures.

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.