Physical Biology Center for Ultrafast Science and Technology, Arthur Amos Noyes Laboratory for Chemical Physics, California Institute of Technology, Pasadena, California 91125, USA.
J Am Chem Soc. 2011 Oct 26;133(42):17072-86. doi: 10.1021/ja207722k. Epub 2011 Oct 5.
Among the macromolecular patterns of biological significance, right-handed α-helices are perhaps the most abundant structural motifs. Here, guided by experimental findings, we discuss both ultrafast initial steps and longer-time-scale structural dynamics of helix-coil transitions induced by a range of temperature jumps in large, isolated macromolecular ensembles of an α-helical protein segment thymosin β(9) (Tβ(9)), and elucidate the comprehensive picture of (un)folding. In continuation of an earlier theoretical work from this laboratory that utilized a simplistic structure-scrambling algorithm combined with a variety of self-avoidance thresholds to approximately model helix-coil transitions in Tβ(9), in the present contribution we focus on the actual dynamics of unfolding as obtained from massively distributed ensemble-convergent MD simulations which provide an unprecedented scope of information on the nature of transient macromolecular structures, and with atomic-scale spatiotemporal resolution. In addition to the use of radial distribution functions of ultrafast electron diffraction (UED) simulations in gaining an insight into the elementary steps of conformational interconversions, we also investigate the structural dynamics of the protein via the native (α-helical) hydrogen bonding contact metric which is an intuitive coarse graining approach. Importantly, the decay of α-helical motifs and the (globular) conformational annealing in Tβ(9) occur consecutively or competitively, depending on the magnitude of temperature jump.
在具有生物学意义的大分子模式中，右手α-螺旋可能是最丰富的结构基序。在这里，我们根据实验发现，讨论了在一系列温度跳跃下，大的、孤立的α-螺旋蛋白质片段胸腺肽β（9）（Tβ（9））的宏观分子聚集体中诱导的螺旋-卷曲转变的超快初始步骤和更长时间尺度的结构动力学，并阐明了（解）折叠的综合图景。在本实验室早期的理论工作的基础上，该理论工作利用了一种简单的结构混淆算法，并结合了各种自回避阈值，来近似模拟 Tβ（9）中的螺旋-卷曲转变，在本研究中，我们专注于从大规模分布的集合收敛 MD 模拟中获得的展开实际动力学，这些模拟提供了关于瞬态大分子结构性质的前所未有的信息范围，并具有原子尺度的时空分辨率。除了使用超快电子衍射（UED）模拟的径向分布函数来深入了解构象转化的基本步骤外，我们还通过原生（α-螺旋）氢键接触度量来研究蛋白质的结构动力学，这是一种直观的粗粒化方法。重要的是，Tβ（9）中α-螺旋基序的衰减和（球形）构象退火连续或竞争发生，这取决于温度跳跃的幅度。
