Induction of Peptide Bond Dipoles Drives Cooperative Helix Formation in the (AAQAA)3 Peptide
Induction of Peptide Bond Dipoles Drives Cooperative Helix Formation in the (AAQAA)3 Peptide
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DOI：
10.1016/j.bpj.2014.06.038
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发表时间：
2014-08-19
影响因子：
3.4
通讯作者：
MacKerell, Alexander D., Jr.
中科院分区：
文献类型：
--
作者：
Huang, Jing;MacKerell, Alexander D., Jr.
协同性是蛋白质二级结构形成的核心特征。然而，人们对这种合作背后的驱动力知之甚少。本研究表明，在包括电子极化率处理在内的经验力场作用下，乙酰基-(AAQAA)(3)- nh2肽中螺旋形成的协同性显著增强。极化模拟得到的螺旋含量与实验测量结果一致，并表明螺旋含量对温度的依赖性比加性模型得到了改善，尽管需要进一步的采样来充分验证这一结论。协同性是通过肽的盘绕状态或长螺旋与相对较少的短螺旋的抽样来表示的。这种协同性与螺旋形成时肽主链的偶极矩增强有关。这些结果表明，基于电子极化性的物理现实处理，极化力场可以更准确地模拟肽折叠协同性。
Cooperativity is a central feature in the formation of secondary structures in proteins. However, the driving forces behind this cooperativity are poorly understood. The present work shows that the cooperativity of helix formation in the acetyl-(AAQAA)(3)-NH2 Peptide is significantly enhanced using an empirical force field that explicitly includes the treatment of electronic polarizability. Polarizable simulations yield helical content consistent with experimental measurements and indicate that the dependence of helical content on temperature is improved over additive models, though further sampling is required to fully validate this conclusion. Cooperativity is indicated by the peptide sampling either the coiled state or long helices with relatively low populations of short helices. The cooperativity is shown to be associated with enhanced dipole moments of the peptide backbone upon helix formation. These results indicate the polarizable force field to more accurately model peptide-folding cooperativity based on its physically realistic treatment of electronic polarizability.