STRUCTURE & DYNAMICS OF CALMODULIN IN SOLUTION: MUSCLE CONTRACTION

为了表征钙调素在溶液中的动力学行为，我们 进行了分子动力学（MD）模拟， Ca 2+负载结构 *（参见参考文献[91]）。 的晶体结构 将钙调蛋白置于半径为44 E的溶剂球中，6 Cl-和 包括22个Na+离子以中和系统并模拟150 mM盐浓度。 原子总数为32，867。 期间 3 ns模拟显示该结构具有大的构象 纳秒时间尺度上的变化。 中央的阿尔法螺旋， 已经显示在钙调蛋白与靶结合时局部解旋 蛋白质，在残基Arg 74附近弯曲和解旋。 我们这样解释 结果作为更广泛的结构中的准备步骤， 在“柔性接头”区域74-82中观察到的过渡 复合体形成时的中心螺旋。 主要的结构变化是 两个Ca 2+结合结构域相对于各自 其他和N-末端结构域中α-螺旋的重排 这使得疏水性靶肽结合位点更多 容易接近 这种结构重排使结构域成为一个 更有利的地位，为目标的结合，准备实现 在钙调蛋白与 肌球蛋白轻链激酶 溶剂结构分析揭示了 蛋白质附近水的流动性不均匀 这可归因于由以下物质施加的疏水效应： 钙调蛋白的靶肽结合位点。

To characterize the dynamic behavior of calmodulin in solution, we have carried out molecular dynamics (MD) simulations of the Ca2+-loaded structure* (see reference [91]). The crystal structure of calmodulin was placed in a solvent sphere of radius 44E, and 6 Cl- and 22 Na+ ions were included to neutralize the system and to model a 150 mM salt concentration. The total number of atoms was 32,867. During the 3 ns simulation the structure exhibits large conformational changes on the nanosecond time scale. The central alpha-helix, which has been shown to unwind locally upon binding of calmodulin to target proteins, bends and unwinds near residue Arg74. We interpret this result as a preparative step in the more extensive structural transition observed in the "flexible linker" region 74-82 of the central helix upon complex formation. The major structural change is a reorientation of the two Ca2+-binding domains with respect to each other and a rearrangement of alpha-helices i n the N-terminus domain which make the hydrophobic target peptide binding site more accessible. This structural rearrangement brings the domains to a more favorable position for target binding, poised to achieve the orientation observed in the complex of calmodulin with myosin-light-chain-kinase. Analysis of solvent structure reveals an inhomogeneity in the mobility of water in the vicinity of the protein which is attributable to the hydrophobic effect exerted by calmodulin's binding sites for target peptides.