Department of Biochemistry and Molecular Biophysics, Washington University, St. Louis, Missouri 63110, USA.
J Phys Chem B. 2010 Mar 4;114(8):2549-64. doi: 10.1021/jp910674d.
Molecular force fields have been approaching a generational transition over the past several years, moving away from well-established and well-tuned, but intrinsically limited, fixed point charge models toward more intricate and expensive polarizable models that should allow more accurate description of molecular properties. The recently introduced AMOEBA force field is a leading publicly available example of this next generation of theoretical model, but to date, it has only received relatively limited validation, which we address here. We show that the AMOEBA force field is in fact a significant improvement over fixed charge models for small molecule structural and thermodynamic observables in particular, although further fine-tuning is necessary to describe solvation free energies of drug-like small molecules, dynamical properties away from ambient conditions, and possible improvements in aromatic interactions. State of the art electronic structure calculations reveal generally very good agreement with AMOEBA for demanding problems such as relative conformational energies of the alanine tetrapeptide and isomers of water sulfate complexes. AMOEBA is shown to be especially successful on protein-ligand binding and computational X-ray crystallography where polarization and accurate electrostatics are critical.
在过去的几年中，分子力场经历了一次代际转变，逐渐摆脱了成熟且经过良好调整但本质上有限的固定点电荷模型，转向更复杂和昂贵的极化模型，以实现更准确的分子性质描述。最近推出的 AMOEBA 力场是下一代理论模型的一个领先的公开示例，但迄今为止，它只得到了相对有限的验证，我们在这里解决了这个问题。我们表明，AMOEBA 力场实际上是对小分子结构和热力学观测值的固定电荷模型的重大改进，特别是尽管需要进一步微调才能描述类似药物的小分子的溶剂化自由能、环境条件以外的动力学特性以及芳香相互作用的可能改进。最先进的电子结构计算表明，对于要求苛刻的问题，如丙氨酸四肽的相对构象能和水硫酸盐配合物的异构体，与 AMOEBA 的结果通常非常吻合。AMOEBA 在蛋白质-配体结合和计算 X 射线晶体学方面表现出色，在这些领域，极化和准确的静电学至关重要。
