Becker O M
Department of Chemical Physics, School of Chemistry, Tel Aviv University, Ramat Aviv, Israel.
Proteins. 1997 Feb;27(2):213-26. doi: 10.1002/(sici)1097-0134(199702)27:2<213::aid-prot8>3.0.co;2-g.
Clustering molecular conformations into "families" is a common procedure in conformational analysis of molecular systems. An implicit assumption which often underlies this clustering approach is that the resulting geometric families reflect the energetic structure of the system's potential energy surface. In a broader context we address the question whether structural similarity is correlated with energy basins, i.e., whether conformations that belong to the same energy basin are also geometrically similar. 'Topological mapping' and principal coordinate projections are used here to address this question and to assess the quality of the 'family clustering' procedure. Applying the analysis to a small tetrapeptide it was found that the general correlation that exists between energy basins and structural similarity is not absolute. Clusters generated by the geometric 'family clustering' procedure do not always reflect the underlying energy basins. In particular it was found that the 'family tree' that is generated by the 'family clustering' procedure is completely inconsistent with its real topological counterpart, the 'disconnectivity' graph of this system. It is also demonstrated that principal coordinate analysis is a powerful visualization technique which, at least for this system, works better when distances are measured in dihedral angle space rather than in cartesian space.
将分子构象聚类成“家族”是分子系统构象分析中的常见步骤。这种聚类方法通常隐含的一个假设是，所得的几何家族反映了系统势能面的能量结构。在更广泛的背景下，我们探讨结构相似性是否与能量盆地相关，即属于同一能量盆地的构象在几何上是否也相似。这里使用“拓扑映射”和主坐标投影来解决这个问题，并评估“家族聚类”程序的质量。将该分析应用于一个小的四肽时发现，能量盆地与结构相似性之间存在的一般相关性并非绝对。由几何“家族聚类”程序生成的簇并不总是反映潜在的能量盆地。特别是发现，由“家族聚类”程序生成的“家族树”与其真实的拓扑对应物，即该系统的“不连通性”图完全不一致。还证明了主坐标分析是一种强大的可视化技术，至少对于这个系统，当在二面角空间而不是笛卡尔空间中测量距离时效果更好。
