An analysis of conformational changes on protein-protein association: implications for predictive docking
An analysis of conformational changes on protein-protein association: implications for predictive docking
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DOI：
10.1093/protein/12.4.271
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发表时间：
1999-04-01
期刊：
影响因子：
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通讯作者：
Sternberg, MJE
中科院分区：
文献类型：
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作者：
Betts, MJ;Sternberg, MJE
测量了39对复杂蛋白质和非结合等价物的构象变化，平均为界面和非界面区域以及单个残基。我们通过比较12对独立求解的相同蛋白质结构中的差异来评估它们的意义，发现刚刚超过一半的结构有一些实质性的整体运动。运动涉及主链和侧链，界面的大变化与复杂的形成密切相关，而暴露的非界面残基的运动是由柔性和无序引起的。酶中界面运动的程度与抑制剂相似。所有8个具有未结合形式结构的复合体(6个酶抑制剂和2个抗体-抗原)都显示出一些显着的界面运动。然而，预测性对接是成功的，即使当一些最大的变化发生时，我们注意到，除了主导这项研究的酶抑制剂之外，系统中的情况可能不同。因此，一般模型是诱导符合的，但由于许多系统中只有有限的构象变化，识别可以被视为一次近似的锁和钥匙。
Conformational changes on complex formation have been measured for 39 pairs of structures of complexed proteins and unbound equivalents, averaged over interface and non-interface regions and for individual residues. We evaluate their significance by comparison with the differences seen in 12 pairs of independently solved structures of identical proteins, and find that just over half have some substantial overall movement. Movements involve main chains as well as side chains, and large changes in the interface are closely involved with complex formation, while those of exposed non-interface residues are caused by flexibility and disorder Interface movements in enzymes are similar in extent to those of inhibitors. All eight of the complexes (six enzyme-inhibitor and two antibody-antigen) that have structures of both components in an unbound form available show some significant interface movement. However; predictive docking is successful even when some of the largest changes occur We note however that the situation may be different in systems other than the enzyme-inhibitors which dominate this study. Thus the general model is induced fit but, because there is only limited conformational change in many systems, recognition can be treated as lock and key to a first approximation.