SIGNIFICANCE OF ROOT-MEAN-SQUARE DEVIATION IN COMPARING 3-DIMENSIONAL STRUCTURES OF GLOBULAR-PROTEINS
SIGNIFICANCE OF ROOT-MEAN-SQUARE DEVIATION IN COMPARING 3-DIMENSIONAL STRUCTURES OF GLOBULAR-PROTEINS
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DOI：
10.1006/jmbi.1994.1017
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发表时间：
1994-01-14
影响因子：
5.6
通讯作者：
CRIPPEN, GM
中科院分区：
文献类型：
--
作者：
MAIOROV, VN;CRIPPEN, GM
在球状蛋白质构象的研究中，人们通常用最佳刚体叠加后的Cα原子坐标的均方根偏差（RMSD）来度量三维结构的相似性。即使当两种蛋白质结构都由具有相同残基数量的单链组成，使得Cα原子的匹配是明显的，也不清楚如何解释RMSD。一个非常大的值意味着它们是不相似的，零意味着它们在构象上是相同的，但是在什么中间值时它们特别相似或明显不相似？虽然在该领域的许多工作人员选择了任意截止，和其他人判断值的RMSD根据观察到的分布随机结构的RMSD，我们提出了一个自我参考，非统计标准。如果两个构象异构体的RMSD小于其中一个构象异构体镜像反转时的RMSD，则认为它们本质相似。因为这里考虑的结构不是任意配置的点原子，但紧凑，球状，多肽链，我们的定义是密切相关的回转半径和整体链折叠模式的相似性。在我们的意义上，强相似意味着回转半径必须几乎相同，原子间距离的均方根偏差与RMSD线性相关，并且两个链必须具有相同的一般折叠。只有当RMSD超过这个水平时，多肽链的一部分才能经历非平凡的重排，同时保持球形。这使我们能够判断蛋白质构象的预测何时是“正确的，除了微小的扰动”，或者何时从NMR实验推导出的蛋白质结构的集合“基本上相互一致”。
In the study of globular protein conformations, one customarily measures the similarity in three-dimensional structure by the root-mean-square deviation (RMSD) of the Cαatomic coordinates after optimal rigid body superposition. Even when the two protein structures each consist of a single chain having the same number of residues so that the matching of Cαatoms is obvious, it is not clear how to interpret the RMSD. A very large value means they are dissimilar, and zero means they are identical in conformation, but at what intermediate values are they particularly similar or clearly dissimilar? While many workers in the field have chosen arbitrary cutoffs, and others have judged values of RMSD according to the observed distribution of RMSD for random structures, we propose a self-referential, non-statistical standard. We take two conformers to be intrinsically similar if their RMSD is smaller than that when one of them is mirror inverted. Because the structures considered here are not arbitrary configurations of point atoms, but are compact, globular, polypeptide chains, our definition is closely related to similarity in radius of gyration and overall chain folding patterns. Being strongly similar in our sense implies that the radii of gyration must be nearly identical, the root-mean-square deviation in interatomic distances is linearly related to RMSD, and the two chains must have the same general fold. Only when the RMSD exceeds this level can parts of the polypeptide chain undergo nontrivial rearrangements while remaining globular. This enables us to judge when a prediction of a protein's conformation is "correct except for minor perturbations", or when the ensemble of protein structures deduced from NMR experiments are "basically in mutual agreement".