Laboratoire de Chimie Physique , Université Paris Sud - CNRS, Université Paris Saclay , 15 Avenue Jean Perrin , 91405 Orsay Cedex , France.
Sorbonne Université, CNRS , Institut Parisien de Chimie Physique et Théorique (IP2CT) , 4 Place Jussieu , F-75005 , Paris , France.
J Chem Theory Comput. 2018 May 8;14(5):2705-2720. doi: 10.1021/acs.jctc.7b01128. Epub 2018 Apr 16.
We report the first parameters of the heme redox cofactors for the polarizable AMOEBA force field in both the ferric and ferrous forms. We consider two types of complexes, one with two histidine side chains as axial ligands and one with a histidine and a methionine side chain as ligands. We have derived permanent multipoles from second-order Møller-Plesset perturbation theory (MP2). The sets of parameters have been validated in a first step by comparison of AMOEBA interaction energies of heme and a collection of biologically relevant molecules with MP2 and Density Functional Theory (DFT) calculations. In a second validation step, we consider interaction energies with large aggregates comprising around 80 HO molecules. These calculations are repeated for 30 structures extracted from semiempirical PM7 DM simulations. Very encouraging agreement is found between DFT and the AMOEBA force field, which results from an accurate treatment of electrostatic interactions. We finally report long (10 ns) MD simulations of cytochromes in two redox states with AMOEBA testing both the 2003 and 2014 AMOEBA water models. These simulations have been carried out with the TINKER-HP (High Performance) program. In conclusion, owing to their ubiquity in biology, we think the present work opens a wide array of applications of the polarizable AMOEBA force field on hemeproteins.
我们报告了在亚铁和高铁形式下，可极化 AMOEBA 力场中血红素氧化还原辅因子的第一个参数。我们考虑了两种类型的配合物，一种具有两个组氨酸侧链作为轴向配体，另一种具有一个组氨酸和一个蛋氨酸侧链作为配体。我们从二阶 Møller-Plesset 微扰理论（MP2）推导出了永久多极矩。在第一步中，我们通过将血红素和一系列具有生物学意义的分子的 AMOEBA 相互作用能与 MP2 和密度泛函理论（DFT）计算进行比较，验证了参数集。在第二步验证中，我们考虑了与包含约 80 个 HO 分子的大聚集体的相互作用能。这些计算针对从半经验 PM7 DM 模拟中提取的 30 个结构重复进行。DFT 和 AMOEBA 力场之间存在非常令人鼓舞的一致性，这归因于对静电相互作用的准确处理。最后，我们使用 AMOEBA 对两种氧化还原状态的细胞色素进行了长达 10 ns 的 MD 模拟，同时测试了 2003 年和 2014 年的 AMOEBA 水模型。这些模拟是使用 TINKER-HP（高性能）程序进行的。总之，由于血红素在生物学中的普遍性，我们认为这项工作为 AMOEBA 力场在血红素蛋白上的广泛应用开辟了道路。
