Navizet Isabelle, Cailliez Fabien, Lavery Richard
Laboratoire de Biochimie Théorique, UPR 9080 CNRS, Institut de Biologie Physico-Chimique, Paris 75005, France.
Biophys J. 2004 Sep;87(3):1426-35. doi: 10.1529/biophysj.104.042085.
It is becoming clear that, in addition to structural properties, the mechanical properties of proteins can play an important role in their biological activity. It nevertheless remains difficult to probe these properties experimentally. Whereas single-molecule experiments give access to overall mechanical behavior, notably the impact of end-to-end stretching, it is currently impossible to directly obtain data on more local properties. We propose a theoretical method for probing the mechanical properties of protein structures at the single-amino acid level. This approach can be applied to both all-atom and simplified protein representations. The probing leads to force constants for local deformations and to deformation vectors indicating the paths of least mechanical resistance. It also reveals the mechanical coupling that exists between residues. Results obtained for a variety of proteins show that the calculated force constants vary over a wide range. An analysis of the induced deformations provides information that is distinct from that obtained with measures of atomic fluctuations and is more easily linked to residue-level properties than normal mode analyses or dynamic trajectories. It is also shown that the mechanical information obtained by residue-level probing opens a new route for defining so-called dynamical domains within protein structures.
越来越清楚的是，除了结构特性外，蛋白质的力学特性在其生物活性中也可能发挥重要作用。然而，通过实验探测这些特性仍然很困难。虽然单分子实验能够揭示整体力学行为，特别是端到端拉伸的影响，但目前尚无法直接获得有关更局部特性的数据。我们提出了一种理论方法，用于在单氨基酸水平上探测蛋白质结构的力学特性。这种方法既可以应用于全原子模型，也可以应用于简化的蛋白质表示模型。这种探测能够得出局部变形的力常数以及指示最小机械阻力路径的变形向量。它还揭示了残基之间存在的机械耦合。对多种蛋白质的计算结果表明，计算出的力常数变化范围很广。对诱导变形的分析提供了与通过原子涨落测量获得的信息不同的信息，并且比正常模式分析或动态轨迹更容易与残基水平的特性联系起来。研究还表明，通过残基水平探测获得的力学信息为定义蛋白质结构内所谓的动态结构域开辟了一条新途径。
