Department of Chemistry , Yale University , New Haven , Connecticut 06520-8107 , United States.
J Chem Theory Comput. 2019 Apr 9;15(4):2734-2742. doi: 10.1021/acs.jctc.9b00054. Epub 2019 Mar 12.
Significant improvements have been made to the OPLS-AA force field for modeling RNA. New torsional potentials were optimized based on density functional theory (DFT) scans at the ωB97X-D/6-311++G(d,p) level for potential energy surfaces of the backbone α and γ dihedral angles. In combination with previously reported improvements for the sugar puckering and glycosidic torsion terms, the new force field was validated through diverse molecular dynamics simulations for RNAs in aqueous solution. Results for dinucleotides and tetranucleotides revealed both accurate reproduction of J couplings from NMR and the avoidance of several unphysical states observed with other force fields. Simulations of larger systems with noncanonical motifs showed significant structural improvements over the previous OPLS-AA parameters. The new force field, OPLS-AA/M, is expected to perform competitively with other recent RNA force fields and to be compatible with OPLS-AA models for proteins and small molecules.
在用于建模 RNA 的 OPLS-AA 力场方面取得了重大进展。新的扭转势基于 ωB97X-D/6-311++G(d,p) 水平的密度泛函理论 (DFT) 扫描进行了优化，用于骨架 α 和 γ 二面角的势能面。与之前报道的糖环构象和糖苷扭转项的改进相结合，新的力场通过水溶液中 RNA 的各种分子动力学模拟得到了验证。二核苷酸和四核苷酸的结果表明，该力场不仅能够准确再现 NMR 中的 J 耦合，还避免了其他力场中观察到的几种非物理状态。具有非规范模体的更大系统的模拟显示出与之前 OPLS-AA 参数相比结构有显著改进。新的力场 OPLS-AA/M 有望与其他最近的 RNA 力场竞争，并与蛋白质和小分子的 OPLS-AA 模型兼容。
