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首页> 外文期刊>Journal of chemical theory and computation: JCTC >AMBER and CHARMM Force Fields Inconsistently Portray the Microscopic Details of Phosphorylation
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AMBER and CHARMM Force Fields Inconsistently Portray the Microscopic Details of Phosphorylation

机译：琥珀和魅力领域不一致地描绘磷酸化的显微镜细节

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Phosphorylation of serine, threonine, and tyrosine is one of the most frequently occurring and crucial post-translational modifications of proteins often associated with important structural and functional changes. We investigated the direct effect of phosphorylation on the intrinsic conformational preferences of amino acids as a potential trigger of larger structural events. We conducted a comparative study of force fields on terminally capped amino acids (dipeptides) as the simplest model for phosphorylation. Our bias-exchange metadynamics simulations revealed that all model dipeptides sampled a great heterogeneity of ensembles affected by introduction of mono- and dianionic phosphate groups. However, the detected changes in populations of backbone conformers and side-chain rotamers did not reveal a strong discriminatory shift in preferences, as could be anticipated for the bulky, charged phosphate group. Furthermore, the AMBER and CHARMM force fields provided inconsistent populations of individual conformers as well as net structural trends upon phosphorylation. Detailed analysis of ensembles revealed competition between hydration and formation of internal hydrogen bonds involving amide hydrogens and the phosphate group. The observed difference in hydration free energy and potential for hydrogen bonding in individual force fields could be attributed to the different partial atomic charges used in each force field and, hence, the different parametrization strategies. Nevertheless, conformational propensities and net structural changes upon phosphorylation are difficult to extract from experimental measurements, and existing experimental data provide limited guidance for force field assessment and further development.
机译：丝氨酸，苏氨酸和酪氨酸的磷酸化是通常与重要的结构和功能变化相关的蛋白质的最常发生和关键的翻译后修饰之一。我们研究了磷酸化对氨基酸的内在构象偏好的直接效应，作为较大的结构事件的潜在触发。我们对末端覆盖氨基酸（二肽）的力场进行了对比较研究，作为磷酸化的最简单模型。我们的偏兑交换元动力学模拟显示，所有模型二肽都采取了通过引入单磷酸酯和Dianionic磷酸盐基团影响的整体的巨大异质性。然而，骨干符合子和侧链旋转器的群体的检测变化没有揭示偏好的强歧视变换，正如庞大的，带电的磷酸盐基团的预期。此外，琥珀和魅力领域提供了个体符合特者的不一致群体以及磷酸化时的净结构趋势。综合分析揭示了酰胺氢和磷酸盐基的水化与内部氢键的形成竞争。在各个力场中的水合自由能和氢键合电势的观察到的差异可归因于每个力场中使用的不同部分原子电荷，因此，不同的参数化策略。然而，从实验测量中难以提取磷酸化对磷酸化的构象性和净结构变化，并且现有的实验数据为力场评估和进一步发展提供有限的指导。

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