Modelling protein docking using shape complementarity, electrostatics and biochemical information
Modelling protein docking using shape complementarity, electrostatics and biochemical information
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DOI：
10.1006/jmbi.1997.1203
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发表时间：
1997-09-12
影响因子：
5.6
通讯作者：
Sternberg, MJE
中科院分区：
文献类型：
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作者：
Gabb, HA;Jackson, RM;Sternberg, MJE
对两类生物分子复合物：六种酶/抑制剂和四种抗体/抗原进行了蛋白质对接研究。10个测试系统中有8个使用了生物分子复合物，其中络合蛋白和非络合蛋白的晶体结构都是可用的。我们的对接实验包括对平移和旋转空间的全局搜索，然后对最佳预测进行细化。利用傅立叶相关理论，根据形状互补性和有利的静电相互作用对势配合物进行评分。由于蛋白质在结合时发生构象变化，因此评分函数必须足够软，才能成功对接未结合的结构。一定程度的表面重叠是可以容忍的，以解释侧链的灵活性。类似地，在静电学中，一种蛋白质的分散点电荷与另一种蛋白质的库仑场的相互作用被测量，而不是精确的原子相互作用。我们使用原生而非复杂形式的蛋白质来测试我们的对接协议，以解决更具科学意义的预测对接问题。在我们所有的测试案例中，正确对接的几何（界面C-alpha RMS偏差小于或等于实验结构的2埃）在平移和旋转空间的全局搜索中被发现，这个列表总是少于250个，通常少于30个。仍然需要不同程度的生化信息来去除大多数不正确对接的配合物。(C) 1997学术出版社有限公司
A protein docking study was performed for two classes of biomolecular complexes: six enzyme/inhibitor and four antibody/antigen. Biomolecular complexes for which crystal structures of both the complexed and uncomplexed proteins are available were used for eight of the ten test systems. Our docking experiments consist of a global search of translational and rotational space followed by refinement of the best predictions. Potential complexes are scored on the basis of shape complementarity and favourable electrostatic interactions using Fourier correlation theory. Since proteins undergo conformational changes upon binding, the scoring function must be sufficiently soft to dock unbound structures successfully. Some degree of surface overlap is tolerated to account for sidechain flexibility. Similarly for electrostatics, the interaction of the dispersed point charges of one protein with the Coulombic field of the other is measured rather than precise atomic interactions. We tested our docking protocol using the native rather than the complexed forms of the proteins to address the more scientifically interesting problem of predictive docking. In all but one of our test cases, correctly docked geometries (interface C-alpha RMS deviation less than or equal to 2 Angstrom from the experimental structure) are found during a global search of translational and rotational space in a list that was always less than 250 complexes and often less than 30. Varying degrees of biochemical information are still necessary to remove most of the incorrectly docked complexes. (C) 1997 Academic Press Limited.