Fushman D, Ohlenschläger O, Rüterjans H
Institut für Biophysikalische Chemie der J.W. Goethe-Universität Frankfurt, Frankfurt am Main.
J Biomol Struct Dyn. 1994 Jun;11(6):1377-402. doi: 10.1080/07391102.1994.10508074.
The results of 1-nanosecond molecular dynamics simulations of the enzyme ribonuclease T1 and its 2'GMP complex in water are presented. A classification of the angular reorientations of the backbone amide groups is achieved via a transformation of NH-vector trajectories into several coordinate frames, thus unravelling contributions of NH-bond librations and backbone dihedral angle fluctuations. The former turned out to be similar for all amides, as characterized by correlation times of librational motions in a subpicosecond scale, angular amplitudes of about 10-12 degrees for out-of-peptide-plane displacements of the NH-bond and 3-5 degrees for the in-plane displacements, whereas the contributions of much slower backbone dihedral angle fluctuations strongly depend on the secondary structure. Correlation functions relevant for NMR were obtained and analyzed utilizing the 'model-free' approach (Lipari, G. and Szabo, A. (1982) J. Am. Chem. Soc. 104, 4546-4559, 4559-4570; Clore et al., (1990) J. Am. Chem. Soc. 112, 4989-4991). The dependence of the amplitude of local motion on the residue location in the backbone is in good agreement with the results of NMR relaxation measurements and X-ray data. The protein dynamics is characterized by a highly restricted local motion of those parts of the backbone with defined secondary structure as well as by a high flexibility in loop regions. The comparison of results derived from different periods of the trajectory (of 50 ps and 1 ns duration, 1000 points sampled) reveals a dependence of the observed dynamic picture on the characteristic time scale of the experimental method used. Comparison of the MD data for the free and liganded enzyme clearly indicates a restriction of the mobility within certain regions of the backbone upon inhibitor binding.
本文展示了在水中对核糖核酸酶T1及其2'GMP复合物进行1纳秒分子动力学模拟的结果。通过将NH向量轨迹转换到几个坐标系中，实现了对主链酰胺基团角重排的分类，从而揭示了NH键摆动和主链二面角波动的贡献。结果表明，所有酰胺的前者相似，其特征在于亚皮秒尺度的摆动运动相关时间、NH键肽平面外位移的角幅度约为10 - 12度以及平面内位移的角幅度为3 - 5度，而慢得多的主链二面角波动的贡献则强烈依赖于二级结构。利用“无模型”方法（Lipari, G.和Szabo, A. (1982) J. Am. Chem. Soc. 104, 4546 - 4559, 4559 - 4570; Clore等人, (1990) J. Am. Chem. Soc. 112, 4989 - 4991）获得并分析了与核磁共振相关的相关函数。局部运动幅度对主链中残基位置的依赖性与核磁共振弛豫测量结果和X射线数据一致。蛋白质动力学的特征是具有确定二级结构的主链部分的局部运动受到高度限制，以及环区域具有高灵活性。对轨迹不同时间段（持续50皮秒和1纳秒，采样1000个点）得出的结果进行比较，揭示了观察到的动力学图像对所用实验方法特征时间尺度的依赖性。游离酶和配体结合酶的分子动力学数据比较清楚地表明，抑制剂结合后主链某些区域的流动性受到限制。
