Structural insights for designed alanine-rich helices: comparing NMR helicity measures and conformational ensembles from molecular dynamics simulation.
Structural insights for designed alanine-rich helices: comparing NMR helicity measures and conformational ensembles from molecular dynamics simulation.
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DOI：
10.1002/bip.21004
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发表时间：
2008-09
期刊：
影响因子：
2.9
通讯作者：
Simmerling, Carlos
中科院分区：
文献类型：
--
作者：
Song, Kun;Stewart, James M.;Fesinmeyer, R. Matthew;Andersen, Niels H.;Simmerling, Carlos
通过实验和分子动力学模拟研究了Ac-ZGG-（KAAAA）3X-NH 2（Z = Y或G，X = A，K，和d-Arg）多肽螺旋倾向的温度依赖性.观察到的绝对螺旋倾向以及相对螺旋含量沿着序列的良好的一致性;计算的自由能景观上的全局最小值对应于从K4 - A18延伸的单个α-螺旋构象，具有一些末端磨损，特别是在C-末端。能量成分分析表明，单螺旋状态具有有利的分子内静电能，由于氢键，而不太有利的双螺旋球状状态具有有利的溶剂化能。中心赖氨酸残基似乎没有增加螺旋度;然而，实验和模拟研究都显示在X = Ala → Lys → d-Arg序列中螺旋度增加。在Ac-（KAAAA）3X-GY-NH 2和（KAAAA）3X-GY-NH 2序列中也通过实验证实了这种C-封端偏好。的C-加帽组，和整个序列中的赖氨酸，在MD衍生的合奏的作用进行了详细分析。
The temperature dependence of helical propensities for the peptides Ac-ZGG-(KAAAA)3X-NH2 (Z = Y or G, X = A, K, and d-Arg) were studied both experimentally and by molecular dynamics simulations. Good agreement is observed in both the absolute helical propensities as well as relative helical content along the sequence; the global minimum on the calculated free energy landscape corresponds to a single α-helical conformation running from K4 – A18 with some terminal fraying, particularly at the C-terminus. Energy component analysis shows that the single helix state has favorable intramolecular electrostatic energy due to hydrogen bonds, and that less-favorable two-helix globular states have favorable solvation energy. The central lysine residues do not appear to increase helicity; however, both experimental and simulation studies show increasing helicity in the series X = Ala → Lys → d-Arg. This C-capping preference was also experimentally confirmed in Ac-(KAAAA)3X-GY-NH2 and (KAAAA)3X-GY-NH2 sequences. The roles of the C-capping groups, and of lysines throughout the sequence, in the MD-derived ensembles are analyzed in detail.
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