ff14SB: Improving the Accuracy of Protein Side Chain and Backbone Parameters from ff99SB.
ff14SB: Improving the Accuracy of Protein Side Chain and Backbone Parameters from ff99SB.
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DOI：
10.1021/acs.jctc.5b00255
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发表时间：
2015-08-11
影响因子：
5.5
通讯作者：
Simmerling C
中科院分区：
文献类型：
--
作者：
Maier JA;Martinez C;Kasavajhala K;Wickstrom L;Hauser KE;Simmerling C
分子力学在原子模拟中具有强大的速度，但是需要精确的力场。琥珀色的FF99SB力场改善了蛋白质的二级结构平衡，而动力学的弱点（如FF99），但在这里已经确定了所有Amino dir dir的副链旋转式和次链二级结构的弱点。从FF94中，与FF99SB相比，获得了所有用于改善参数的训练集，以改善所有氨基酸的转移。 B.我们还借此机会与FF99SB相比，对φ和ψ参数的多个小调整的经验调整是针对NMR标量偶联数据的多次调整和侧链修改（以下称为FF14SB）不仅可以更好地再现其基准，而且改善了小胡椒中的二级结构含量，并在溶液中繁殖NMRχ1标量偶联测量值，我们还讨论了Amber FF12SB参数，包括FF14S的预定版本。
Molecular mechanics is powerful for its speed in atomistic simulations, but an accurate force field is required. The Amber ff99SB force field improved protein secondary structure balance and dynamics from earlier force fields like ff99, but weaknesses in side chain rotamer and backbone secondary structure preferences have been identified. Here, we performed a complete refit of all amino acid side chain dihedral parameters, which had been carried over from ff94. The training set of conformations included multidimensional dihedral scans designed to improve transferability of the parameters. Improvement in all amino acids was obtained as compared to ff99SB. Parameters were also generated for alternate protonation states of ionizable side chains. Average errors in relative energies of pairs of conformations were under 1.0 kcal/mol as compared to QM, reduced 35% from ff99SB. We also took the opportunity to make empirical adjustments to the protein backbone dihedral parameters as compared to ff99SB. Multiple small adjustments of φ and ψ parameters were tested against NMR scalar coupling data and secondary structure content for short peptides. The best results were obtained from a physically motivated adjustment to the φ rotational profile that compensates for lack of ff99SB QM training data in the β-ppII transition region. Together, these backbone and side chain modifications (hereafter called ff14SB) not only better reproduced their benchmarks, but improved secondary structure content in small peptides, and reproduction of NMR χ1 scalar coupling measurements for proteins in solution. We also discuss the Amber ff12SB parameter set, a preliminary version of ff14SB that includes most of its improvements.