Cerutti David S, Swope William C, Rice Julia E, Case David A
Department of Chemistry and Chemical Biology and BioMaPS Institute, Rutgers University , 610 Taylor Road, Piscataway, New Jersey 08854-8066, United States.
J Chem Theory Comput. 2014 Oct 14;10(10):4515-4534. doi: 10.1021/ct500643c. Epub 2014 Sep 18.
We present the ff14ipq force field, implementing the previously published IPolQ charge set for simulations of complete proteins. Minor modifications to the charge derivation scheme and van der Waals interactions between polar atoms are introduced. Torsion parameters are developed through a generational learning approach, based on gas-phase MP2/cc-pVTZ single-point energies computed of structures optimized by the force field itself rather than the quantum benchmark. In this manner, we sacrifice information about the true quantum minima in order to ensure that the force field maintains optimal agreement with the MP2/cc-pVTZ benchmark for the ensembles it will actually produce in simulations. A means of making the gas-phase torsion parameters compatible with solution-phase IPolQ charges is presented. The ff14ipq model is an alternative to ff99SB and other Amber force fields for protein simulations in programs that accommodate pair-specific Lennard-Jones combining rules. The force field gives strong performance on α-helical and β-sheet oligopeptides as well as globular proteins over microsecond time scale simulations, although it has not yet been tested in conjunction with lipid and nucleic acid models. We show how our choices in parameter development influence the resulting force field and how other choices that may have appeared reasonable would actually have led to poorer results. The tools we developed may also aid in the development of future fixed-charge and even polarizable biomolecular force fields.
我们展示了ff14ipq力场，它采用了先前发表的用于完整蛋白质模拟的IPolQ电荷集。对电荷推导方案和极性原子之间的范德华相互作用进行了微小修改。扭转参数是通过一种世代学习方法开发的，该方法基于由力场本身而非量子基准优化的结构所计算出的气相MP2/cc-pVTZ单点能量。通过这种方式，我们牺牲了有关真实量子极小值的信息，以确保力场与它在模拟中实际产生的系综的MP2/cc-pVTZ基准保持最佳一致性。提出了一种使气相扭转参数与溶液相IPolQ电荷兼容的方法。ff14ipq模型是ff99SB和其他Amber力场在适用于特定对Lennard-Jones组合规则的程序中进行蛋白质模拟的替代方案。在微秒时间尺度的模拟中，该力场在α-螺旋和β-折叠寡肽以及球状蛋白质上表现出色，尽管它尚未与脂质和核酸模型结合进行测试。我们展示了我们在参数开发中的选择如何影响所得的力场，以及其他看似合理的选择实际上会如何导致更差的结果。我们开发的工具也可能有助于未来固定电荷甚至可极化生物分子力场的开发。
