a School of Chemistry , Cardiff University , Park Place, Cardiff CF10 3AT , UK.
b Department of Chemistry , University of Warwick , Gibbet Hill, Coventry CV4 7AL , UK.
J Biomol Struct Dyn. 2018 Apr;36(5):1145-1153. doi: 10.1080/07391102.2017.1313780. Epub 2017 Apr 19.
Ligand field molecular mechanics (LFMM) parameters have been benchmarked for copper (II) bound to the amyloid-β peptide fragment. Several density functional theory (DFT) optimised small test models, representative of different possible copper coordination modes, have been used to test the accuracy of the LFMM copper bond lengths and angles, resulting in errors typically less than 0.1 Å and 5°. Ligand field molecular dynamics (LFMD) simulations have been carried out on the copper bound amyloid-β peptide and snapshots extracted from the subsequent trajectory. Snapshots have been optimised using DFT and the semi-empirical PM7 method resulting in good agreement against the LFMM calculated geometry. Analysis of substructures within snapshots shows that the larger contribution of geometrical difference, as measured by RMSD, lies within the peptide backbone, arising from differences in DFT and AMBER, and the copper coordination sphere is reproduced well by LFMM. PM7 performs excellently against LFMM with an average RMSD of 0.2 Å over 21 tested snapshots. Further analysis of the LFMD trajectory shows that copper bond lengths and angles have only small deviations from average values, with the exception of a carbonyl moiety from the N-terminus, which can act as a weakly bound fifth ligand.
配体场分子力学 (LFMM) 参数已针对与淀粉样β肽片段结合的铜 (II) 进行了基准测试。使用了几种密度泛函理论 (DFT) 优化的小型测试模型，代表不同可能的铜配位模式，以测试 LFMM 铜键长和角度的准确性，结果通常误差小于 0.1 Å 和 5°。对结合铜的淀粉样β肽进行了配体场分子动力学 (LFMD) 模拟，并从随后的轨迹中提取快照。使用 DFT 和半经验 PM7 方法对快照进行了优化，结果与 LFMM 计算的几何形状吻合良好。对快照中亚结构的分析表明，RMSD 测量的几何差异较大的部分位于肽骨架内，这是由于 DFT 和 AMBER 之间的差异引起的，而 LFMM 很好地再现了铜配位球。PM7 对 LFMM 的表现非常出色，在 21 个测试快照中平均 RMSD 为 0.2 Å。对 LFMD 轨迹的进一步分析表明，铜键长和角度只有很小的偏离平均值，除了 N 端的羰基部分外，它可以作为一个弱结合的第五配体。
