Universal Implementation of a Residue-Specific Force Field Based on CMAP Potentials and Free Energy Decomposition

作者：Kang, Wei; Jiang, Fan^*; Wu, Yun-Dong

来源：Journal of Chemical Theory and Computation, 2018, 14(8): 4474-4486.

DOI：10.1021/acs.jctc.8b00285

• MOLECULAR-DYNAMICS SIMULATIONS
• INTRINSICALLY DISORDERED PROTEINS
• BETA-HAIRPIN FORMATION
• STRUCTURE PREDICTION
• SIDE-CHAIN
• UNFOLDED STATE
• AMBER FF99SB
• WATER MODEL
• BACKBONE
• CHARMM

The coupling between neighboring backbone phi and Psi dihedral angles (torsions) has been well appreciated in protein force field development, as in correction map (CMAP) potentials. However, although preferences of backbone torsions are significantly affected by side-chain conformation, there has been no easy way to optimize this coupling. Herein, we prove that the three-dimensional (3D) free energy hypersurface of joint (phi, Psi, chi(1)) torsions can be decomposed into three separated 2D surfaces. Thus, each of the 2D torsional surfaces can be efficiently and automatically optimized using a CMAP potential. This strategy is then used to reparameterize an AMBER force field such that the resulting chi(1)-dependent backbone conformational preference can agree excellently with the reference protein coil library statistics. In various validation simulations (including the folding of seven peptides/proteins, backbone dynamics of three folded proteins, and two intrinsically disordered peptides), the new RSFF2C (residue-specific force field with CMAP potentials) force field gives similar or better performance compared with RSFF2. This strategy can be used to implement our RSFF force fields into a variety of molecular dynamics packages easily.

• 出版日期2018-8
• 单位北京大学