Unfolding of α-helical 20-residue poly-glutamic acid analyzed by multiple runs of canonical molecular dynamics simulations.
Unfolding of α-helical 20-residue poly-glutamic acid analyzed by multiple runs of canonical molecular dynamics simulations.
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作者：
Ogasawara N;Kasahara K;Iwai R;Takahashi T
阐明短肽螺旋线圈转变的分子机制是物理化学中一个长期存在的难题。虽然聚谷氨酸（PGA）的螺旋圈跃迁已被广泛研究，但其展开过程的分子细节仍不清楚。为了在原子分辨率上研究其螺旋展开过程，我们对20个残基的PGA进行了19 μs的全原子正则分子动力学模拟。在从α-螺旋构象开始的28个模拟中，均显示了末端残基解绕触发的展开过程，而不是链中部区域的扭结和解绕触发的展开过程。没有观察到先前实验推测的螺旋-线圈-螺旋构象。比较N端和c端，后者往往不稳定，容易展开。虽然在链的n端、中间和c端区域螺旋伸长的概率几乎相同，但在c端区域螺旋的解绕更加丰富。旋转和310螺旋构象是α-螺旋形成和变形的动力学中间产物，这与以往阿拉基肽的计算研究一致。
Elucidating the molecular mechanism of helix–coil transitions of short peptides is a long-standing conundrum in physical chemistry. Although the helix–coil transitions of poly-glutamic acid (PGA) have been extensively studied, the molecular details of its unfolding process still remain unclear. We performed all-atom canonical molecular dynamics simulations for a 20-residue PGA, over a total of 19 μs, in order to investigate its helix-unfolding processes in atomic resolution. Among the 28 simulations, starting with the α-helical conformation, all showed an unfolding process triggered by the unwinding of terminal residues, rather than by kinking and unwinding of the middle region of the chain. The helix–coil–helix conformation which is speculated by the previous experiments was not observed. Upon comparison between the N- and C-termini, the latter tended to be unstable and easily unfolded. While the probabilities of helix elongation were almost the same among the N-terminal, middle, and C-terminal regions of the chain, unwinding of the helix was enriched at the C-terminal region. The turn and 310-helix conformations were kinetic intermediates in the formation and deformation of α-helix, consistent with the previous computational studies for Ala-based peptides.
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DOI：
10.1073/pnas.96.13.7232
发表时间：
1999-06-22
影响因子：
11.1
作者：
Clarke, DT;Doig, AJ;Jones, GR
通讯作者：
Jones, GR
影响因子：
2.9
作者：
Finke, John M.;Jennings, Patricia A.;Winkler, Jay R.
通讯作者：
Winkler, Jay R.
影响因子：
15
作者：
Kimura, T;Takahashi, S;Morishima, I
通讯作者：
Morishima, I
影响因子：
15
作者：
Spek, EJ;Olson, CA;Kallenbach, NR
通讯作者：
Kallenbach, NR
影响因子：
14.8
作者：
Greenfield, Norma J.
通讯作者：
Greenfield, Norma J.