TCB Publications - Paper Request

Wei Han and Klaus Schulten. Further optimization of a hybrid united-atom and coarse-grained force field for folding simulations: Improved backbone hydration and interactions between charged side chains. Journal of Chemical Theory and Computation, 8:4413-4424, 2012.

HAN2012 PACE, a hybrid force field which couples united-atom protein models with coarse-grained (CG) solvent (JCTC, 2010, 6, 3373), has been further optimized, aiming to improve its efficiency for folding simulations. Backbone hydration parameters have been re-optimized based on hydration free energies of polyalanyl peptides through atomistic simulations. Also, atomistic partial charges from all-atom force fields were combined with PACE in order to provide a more realistic description of interactions between charged groups. Using replica exchange molecular dynamics (REMD), ab initio folding using the new PACE has been achieved for seven small proteins (16-23 residues) with different structural motifs. Experimental data about folded states, such as their stability at room temperature, melting point and NMR NOE constraints, were also well reproduced. Moreover, a systematic comparison of folding kinetics at room temperature has been made with experiments, through standard MD simulations, showing that the new PACE may speed up the actual folding kinetics 5-10 times. Together with the computational speedup benefited from coarse-graining, the force field provides opportunities to study folding mechanisms. In particular, we used the new PACE to fold a 73-residue protein, $\alpha$3D, in multiple 10-30 microsecond simulations, to its native states (C$\alpha$ RMSD $\sim$0.34 nm). Our results suggest the potential applicability of the new PACE for the study of folding and dynamics of proteins.

Request Paper

Full Name
Email Address
Type the number seven in the box