Incorporating polarizability of backbone hydrogen bonds improved folding of short α-helical peptides
Incorporating polarizability of backbone hydrogen bonds improved folding of short α-helical peptides
复制标题
结合主链氢键的极化性改善了短α螺旋肽的折叠
DOI：
10.1016/j.bpj.2019.10.020
复制
发表时间：
2019
影响因子：
3.4
通讯作者：
Yew Mun Yip
中科院分区：
文献类型：
--
作者：
Dawei Zhang;Raudah Lazim;Yew Mun Yip
力场的可靠性是蛋白质折叠模拟的一个重要方面。在这项工作中，我们引入了一种新开发的动态电荷更新方案，称为极化结构特定主干电荷（PSBC）模型。 PSBC模型的设计目的是通过在折叠模拟过程中更新主链氢键供体和受体原子的部分电荷，将主链氢键的极化性构建到力场中。该实现的目的是模拟折叠过程中周围蛋白质的异质性。使用可极化 (PSBC) 和不可极化 (Amber03) 力场进行多个单轨迹分子动力学模拟来折叠聚丙氨酸肽，即 ER (Ac-A(EAAAR)3A-NH2)。通过PSBC模型，ER被折叠成螺旋肽，其螺旋含量与实验吻合良好。使用上述力场进行的模拟之间的比较清楚地表明静电极化效应在短α-螺旋肽折叠中的重要性。通过折叠另外两个具有不同螺旋度的短肽，进一步验证了 PSBC 模型。
Reliability of force fields is an essential aspect of protein-folding simulation. In this work, we introduced a newly developed on-the-fly charge-updating scheme called the polarized structure-specific backbone charge (PSBC) model. The PSBC model was designed with the purpose of building the polarizability of backbone hydrogen bonds into the force field by updating the partial charges of backbone hydrogen-bond donor and acceptor atoms during folding simulation. This implementation was intended to mimic the heterogeneity of the protein surrounding during folding. Multiple single-trajectory molecular dynamics simulations were performed to fold a polyalanine peptide, namely ER (Ac-A(EAAAR)3A-NH2), using both polarizable (PSBC) and nonpolarizable (Amber03) force fields. Through the PSBC model, ER was folded into a helical peptide with helix content that agrees well with experiments. Comparison between simulations performed using the aforementioned force fields demonstrably showed the importance of electrostatic polarization effect in the folding of the shortα-helical peptide. The PSBC model was further validated by folding two other short peptides with different helicities.