Accurate modeling of protein conformation by automatic segment matching

作者：Michael D. Levitt · 发表于：Journal of Molecular Biology · 年份：1992 · DOI：10.1016/0022-2836(92)90964-l · 被引用次数：561 · 研究领域：Protein Structure and Dynamics、Enzyme Structure and Function、Computational Drug Discovery Methods

Segment match modeling uses a data base of highly refined known protein X-ray structures to build an unknown target structure from its amino acid sequence and the atomic coordinates of a few of its atoms (generally only the C alpha atoms). The target structure is first broken into a set of short segments. The data base is then searched for matching segments, which are fitted onto the framework of the target structure. Three criteria are used for choosing a matching data base segment: amino acid sequence similarity, conformational similarity (atomic co-ordinates), and compatibility with the target structure (van der Waals' interactions). The new method works surprisingly well: for eight test proteins ranging in size from 46 to 323 residues, the all-atom root-mean-square deviation of the modeled structures is between 0.93 A and 1.73 A (the average is 1.26 A). Deviations of this magnitude are comparable with those found for protein co-ordinates before and after refinement against X-ray data or for co-ordinates of the same protein in different crystal packings. These results are insensitive to errors in the C alpha positions or to missing C alpha atoms: accurate models can be built with C alpha errors of up to 1 A or by using only half the C alpha atoms. The fit to the X-ray structures is improved significantly by building several independent models based on different random choices and then averaging co-ordinates; this novel concept has general implications for other modeling ta...