Examining the Refolding of Perturbed Protein Structure Intermediates using Various Molecular Mechanics Force Fields
Examining the Refolding of Perturbed Protein Structure Intermediates using Various Molecular Mechanics Force Fields
复制标题
使用各种分子力学力场检查扰动蛋白质结构中间体的重折叠
DOI：
10.1016/j.bpj.2018.11.2330
复制
发表时间：
2019
影响因子：
3.4
通讯作者：
Marszalek, Piotr E.
中科院分区：
文献类型：
--
作者：
Wang, David;Marszalek, Piotr E.
分子动力学模拟可以预测蛋白质在全原子分辨率下的折叠轨迹，从而提供关于折叠过程的信息，这是很难通过实验获得的。然而，如果分子力学力场被错误地参数化，分子动力学模拟可能无法准确地预测折叠中间体和整体折叠轨迹。因此，基于力谱数据的实验已知蛋白质折叠中间体可能被证明是验证分子动力学模拟折叠蛋白质的能力的有用工具。我们使用原子力光谱数据建立了Titin I91(I27)结构域和共识Ankyrin重复结构NI3C的扰动中间体模型。然后，我们使用六种不同的力场/水模型组合对中间体进行了折叠模拟。在这样做的过程中，我们观察到没有二面体校正力场的Charmm22∗、琥珀FB15和琥珀FF14SB具有最容易的复性这两种蛋白质中间体的时间。此外，还观察到对琥珀ff14Sb力场的二面体校正阻止了这两个中间体的及时折叠。这些结果表明，侧链扭转角的参数化可以显著地帮助蛋白质结构的折叠。此外，结果表明，二面角的特别调整可能会阻碍折叠轨迹的预测。
Molecular dynamics simulations allow for the prediction of protein folding trajectories in all-atom resolution, thereby providing information about the folding process that is difficult to obtain experimentally. If the molecular mechanics force field is incorrectly parameterized however, molecular dynamics simulations may fail to accurately predict folding intermediates and the overall folding trajectory. Therefore, experimentally known protein refolding intermediates based on force spectroscopy data may prove to be a helpful tool in validating the ability of molecular dynamics simulations to refold proteins. We created models of the perturbed intermediates of titin I91 (I27) domain and consensus ankyrin repeat structure, NI3C, using atomic force spectroscopy data. We then conducted refolding simulations of the intermediates using six different force field/water model combinations. In doing so, we observed that the Charmm22∗, Amber fb15, and Amber ff14SB without dihedral correction force fields had the easiest time refolding both protein intermediates. Additionally, it was observed that the dihedral correction to the Amber ff14SB force field prevents the timely refolding of both intermediates. These results suggest that the parameterization of side chain torsion angles can significantly help the refolding of protein structures. Additionally, the results imply that the ad hoc adjustment of dihedral angles may impede folding trajectory predictions.