Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore, 637371, Singapore.
Proteins. 2013 Sep;81(9):1610-20. doi: 10.1002/prot.24319. Epub 2013 Jun 17.
In this work, we report the ab initio folding of three different extended helical peptides namely 2khk, N36, and C34 through conventional molecular dynamics simulation at room temperature using implicit solvation model. Employing adaptive hydrogen bond specific charge (AHBC) scheme to account for the polarization effect of hydrogen bonds established during the simulation, the effective folding of the three extended helices were observed with best backbone RMSDs in comparison to the experimental structures over the helical region determined to be 1.30 Å for 2khk, 0.73 Å for N36 and 0.72 Å for C34. In this study, 2khk will be used as a benchmark case serving as a means to compare the ability of polarized (AHBC) and nonpolarized force field in the folding of an extended helix. Analyses conducted revealed the ability of the AHBC scheme in effectively folding the extended helix by promoting helix growth through the stabilization of backbone hydrogen bonds upon formation during the folding process. Similar observations were also noted when AHBC scheme was employed during the folding of C34 and N36. However, under Amber03 force field, helical structures formed during the folding of 2khk was not accompanied by stabilization thus highlighting the importance of electrostatic polarization in the folding of helical structures.
在这项工作中，我们通过室温下的传统分子动力学模拟，使用隐式溶剂模型，报告了三种不同的扩展螺旋肽 2khk、N36 和 C34 的从头折叠。通过自适应氢键特定电荷 (AHBC) 方案来考虑在模拟过程中建立的氢键的极化效应，与实验结构相比，三个扩展螺旋的有效折叠在螺旋区域的最佳主链 RMSD 为 2khk 为 1.30 Å，N36 为 0.73 Å，C34 为 0.72 Å。在这项研究中，2khk 将作为基准案例，用于比较极化 (AHBC) 和非极化力场在扩展螺旋折叠中的能力。分析表明，AHBC 方案能够通过在折叠过程中形成时稳定骨架氢键来促进螺旋生长，从而有效地折叠扩展螺旋。当在 C34 和 N36 的折叠过程中使用 AHBC 方案时，也观察到了类似的现象。然而，在 Amber03 力场下，2khk 折叠过程中形成的螺旋结构没有得到稳定，这突出了静电极化在螺旋结构折叠中的重要性。
