A point‐charge force field for molecular mechanics simulations of proteins based on condensed‐phase quantum mechanical calculations

作者：Yong Duan, Chun Wu, Shibasish Chowdhury, Mathew C. Lee, Guoming Xiong, Wei Zhang, Rong Yang, Piotr Cieplak, Ray Luo, Tai‐Sung Lee, James W. Caldwell, Junmei Wang, Peter A. Kollman · 发表于：Journal of Computational Chemistry · 年份：2003 · DOI：10.1002/jcc.10349 · 被引用次数：4514 · 研究领域：Protein Structure and Dynamics、DNA and Nucleic Acid Chemistry、Enzyme Structure and Function

Molecular mechanics models have been applied extensively to study the dynamics of proteins and nucleic acids. Here we report the development of a third-generation point-charge all-atom force field for proteins. Following the earlier approach of Cornell et al., the charge set was obtained by fitting to the electrostatic potentials of dipeptides calculated using B3LYP/cc-pVTZ//HF/6-31G** quantum mechanical methods. The main-chain torsion parameters were obtained by fitting to the energy profiles of Ace-Ala-Nme and Ace-Gly-Nme di-peptides calculated using MP2/cc-pVTZ//HF/6-31G** quantum mechanical methods. All other parameters were taken from the existing AMBER data base. The major departure from previous force fields is that all quantum mechanical calculations were done in the condensed phase with continuum solvent models and an effective dielectric constant of epsilon = 4. We anticipate that this force field parameter set will address certain critical short comings of previous force fields in condensed-phase simulations of proteins. Initial tests on peptides demonstrated a high-degree of similarity between the calculated and the statistically measured Ramanchandran maps for both Ace-Gly-Nme and Ace-Ala-Nme di-peptides. Some highlights of our results include (1) well-preserved balance between the extended and helical region distributions, and (2) favorable type-II poly-proline helical region in agreement with recent experiments. Backward compatibility between the new and Cornel...