Department of Physics, Drexel University, Philadelphia, Pennsylvania 19104, United States.
Department of Chemistry, Drexel University, Philadelphia, Pennsylvania 19104, United States.
J Phys Chem B. 2024 Jun 27;128(25):6217-6231. doi: 10.1021/acs.jpcb.4c02278. Epub 2024 Jun 15.
Molecular dynamics (MD) is a great tool for elucidating conformational dynamics of proteins and peptides in water at the atomistic level that often surpasses the level of detail available experimentally. Structure predictions, however, are limited by the accuracy of the underlying MD force field. This limitation is particularly stark in the case of intrinsically disordered peptides and proteins, which are characterized by solvent-accessible and disordered peptide regions and domains. Recent studies show that most additive MD force fields, including CHARMM36m, do not reproduce the intrinsic conformational distributions of guest amino acid residues x in cationic GxG peptides in water in line with experimental data. Positing that a lack of polarizability in additive MD force fields may be the culprit for the reported discrepancies, we here examine the conformational dynamics of guest glycine and alanine residues in cationic GxG peptides in water using two polarizable MD force fields, CHARMM Drude and AMOEBA. Our results indicate that while AMOEBA captures the experimental data better than CHARMM Drude, neither of the two polarizable force fields offers an improvement of the Ramachandran distributions of glycine and alanine residues in cationic GGG and GAG peptides, respectively, over CHARMM36m.
分子动力学（MD）是一种很好的工具，可以在原子水平上阐明蛋白质和肽在水中的构象动力学，其详细程度通常超过实验水平。然而，结构预测受到基础 MD 力场准确性的限制。在固有无序的肽和蛋白质的情况下，这种限制尤为明显，这些肽和蛋白质的特点是溶剂可及和无序的肽区域和结构域。最近的研究表明，大多数加和 MD 力场，包括 CHARMM36m，都不能根据实验数据复制阳离子 GxG 肽中氨基酸残基 x 的固有构象分布。假设加和 MD 力场中缺乏极化率可能是导致报告差异的原因，我们在这里使用两种极化 MD 力场，CHARMM Drude 和 AMOEBA，研究阳离子 GxG 肽中氨基酸残基的构象动力学。我们的结果表明，虽然 AMOEBA 比 CHARMM Drude 更好地捕捉实验数据，但这两种极化力场都没有改善阳离子 GGG 和 GAG 肽中甘氨酸和丙氨酸残基的 Ramachandran 分布，与 CHARMM36m 相比。
