Wriggers W, Schulten K
Department of Physics, University of Illinois at Urbana-Champaign 61801, USA.
Proteins. 1997 Sep;29(1):1-14.
The activity of many proteins induces conformational transitions by hinge-bending, which involves the movement of relatively rigid parts of a protein about flexible joints. We present an algorithm to identify and visualize the movements of rigid domains about common hinges in proteins. In comparing two structures, the method partitions a protein into domains of preserved geometry. The domains are extracted by an adaptive selection procedure using least-squares fitting. The user can maintain the spatial connectivity of the domains and filter significant structural differences (domain movements) from noise in the compared sets of atomic coordinates. The algorithm subsequently characterizes the relative movements of the found domains by effective rotation axes (hinges). The method is applied to several known instances of domain movements in protein structures, namely, in lactoferrin, hexokinase, actin, the extracellular domains of human tissue factor, and the receptor of human growth factor. The results are visualized with the molecular graphics package VMD (Humphrey et al., J. Mol. Graphics 14(1):33-38, 1996). Applications of the algorithm to the analysis of conformational changes in proteins and to biomolecular docking are discussed.
许多蛋白质的活性通过铰链弯曲诱导构象转变，这涉及蛋白质相对刚性部分围绕柔性关节的移动。我们提出了一种算法，用于识别和可视化蛋白质中刚性结构域围绕共同铰链的运动。在比较两个结构时，该方法将蛋白质划分为具有保留几何形状的结构域。这些结构域通过使用最小二乘法拟合的自适应选择程序提取。用户可以保持结构域的空间连通性，并从比较的原子坐标集中的噪声中过滤出显著的结构差异（结构域运动）。该算法随后通过有效旋转轴（铰链）表征所发现结构域的相对运动。该方法应用于蛋白质结构中几个已知的结构域运动实例，即乳铁蛋白、己糖激酶、肌动蛋白、人组织因子的细胞外结构域和人生长因子的受体。结果用分子图形软件包VMD（Humphrey等人，《分子图形学杂志》14(1):33 - 38，1996）进行可视化。讨论了该算法在蛋白质构象变化分析和生物分子对接中的应用。
