Zagrovic Bojan, Jayachandran Guha, Millett Ian S, Doniach Sebastian, Pande Vijay S
Department of Chemistry and Applied Biosciences, Laboratory of Physical Chemistry, ETH Hönggerberg, Zürich 8093, Switzerland.
J Mol Biol. 2005 Oct 21;353(2):232-41. doi: 10.1016/j.jmb.2005.08.053.
Using synchrotron radiation and the small-angle X-ray scattering technique we have measured the radii of gyration of a series of alanine-based alpha-helix-forming peptides of the composition Ace-(AAKAA)(n)-GY-NH(2), n=2-7, in aqueous solvent at 10(+/-1) degrees C. In contrast to other techniques typically used to study alpha-helices in isolation (such as nuclear magnetic resonance and circular dichroism), small-angle X-ray scattering reports on the global structure of a molecule and, as such, provides complementary information to these other, more sequence-local measuring techniques. The radii of gyration that we measure are, except for the 12-mer, lower than the radii of gyration of ideal alpha-helices or helices with frayed ends of the equivalent sequence-length. For example, the measured radius of gyration of the 37-mer is 14.2(+/-0.6)A, which is to be compared with the radius of gyration of an ideal 37-mer alpha-helix of 17.6A. Attempts are made to analyze the origin of this discrepancy in terms of the analytical Zimm-Bragg-Nagai (ZBN) theory, as well as distributed computing explicit solvent molecular dynamics simulations using two variants of the AMBER force-field. The ZBN theory, which treats helices as cylinders connected by random walk segments, predicts markedly larger radii of gyration than those measured. This is true even when the persistence length of the random walk parts is taken to be extremely short (about one residue). Similarly, the molecular dynamics simulations, at the level of sampling available to us, give inaccurate values of the radii of gyration of the molecules (by overestimating them by around 25% for longer peptides) and/or their helical content. We conclude that even at the short sequences examined here (< or =37 amino acid residues), these alpha-helical peptides behave as fluctuating semi-broken rods rather than straight cylinders with frayed ends.
我们使用同步辐射和小角X射线散射技术，在10（±1）℃的水性溶剂中测量了一系列组成Ace-(AAKAA)(n)-GY-NH₂（n = 2 - 7）的基于丙氨酸的α-螺旋形成肽的回转半径。与通常用于单独研究α-螺旋的其他技术（如核磁共振和圆二色性）不同，小角X射线散射报告的是分子的整体结构，因此为这些其他更多基于序列局部测量的技术提供了补充信息。我们测量的回转半径，除了12聚体，都低于理想α-螺旋或具有等效序列长度且末端磨损的螺旋的回转半径。例如，37聚体的测量回转半径为14.2（±0.6）Å，与之相比，理想的37聚体α-螺旋的回转半径为17.6 Å。我们尝试根据解析的齐姆-布拉格-永井（ZBN）理论以及使用AMBER力场的两种变体进行分布式计算显式溶剂分子动力学模拟来分析这种差异的来源。ZBN理论将螺旋视为由随机游走段连接的圆柱体，预测的回转半径明显大于测量值。即使将随机游走部分的持久长度设为极短（约一个残基），情况也是如此。同样，在我们可用的采样水平下，分子动力学模拟给出的分子回转半径值不准确（对于较长的肽，高估约25%）和/或其螺旋含量不准确。我们得出结论，即使在此处研究的短序列（≤37个氨基酸残基）中，这些α-螺旋肽的行为也像是波动的半断杆，而不是末端磨损的直圆柱体。
