MOLECULAR-DYNAMICS SIMULATION OF THE DOCKING OF SUBSTRATES TO PROTEINS
MOLECULAR-DYNAMICS SIMULATION OF THE DOCKING OF SUBSTRATES TO PROTEINS
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DOI：
10.1002/prot.340190303
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发表时间：
1994-07-01
期刊：
影响因子：
--
通讯作者：
BERENDSEN, HJC
中科院分区：
文献类型：
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作者：
DINOLA, A;ROCCATANO, D;BERENDSEN, HJC
描述了一种简单的方法，通过分子动力学模拟的修改来执行底物与蛋白质的对接或探针与受体分子的对接。该方法包括将基板的质心运动与其内部运动和旋转运动分开，以及针对基板的两种类型的运动和接收器的运动单独耦合到不同的热浴。因此，对于这三种类型的运动，耦合到浴的温度和时间常数可以任意变化，允许冷冻或柔性接收器，并允许控制搜索速率而不干扰内部结构。此外，在底物和蛋白质之间应用了额外的排斥项来平滑相互作用。该方法适用于将模型基质对接到模型表面上，以及将磷酸胆碱对接到免疫球蛋白McPC603上，在这两种情况下都使用冷冻受体。使用1300-1700 K范围内的底物平移温度和底物内部自由度的室温，获得有效的非捕获探索性搜索（“直升机视图”），其访问正确的结合位点。然后可以通过单独搜索或动态模拟退火进一步研究低能量构象。在这两种情况下都确定了正确的最小值。讨论了使用柔性受体的可能性。 (C) 1991 Wiley-Liss, Inc.
A simple method is described to perform docking of subtrates to proteins or probes to receptor molecules by a modification of molecular dynamics simulations. The method consists of a separation of the center-of-mass motion of the substrate from its internal and rotational motions, and a separate coupling to different thermal baths for both types of motion of the substrate and for the motion of the receptor. Thus the temperatures and the time constants of coupling to the baths can be arbitrarily varied for these three types of motion, allowing either a frozen or a flexible receptor and allowing control of search rate without disturbance of internal structure. In addition, an extra repulsive term between substrate and protein was applied to smooth the interaction. The method was applied to a model substrate docking onto a model surface, and to the docking of phosphocholine onto immunoglobulin McPC603, in both cases with a frozen receptor. Using translational temperatures of the substrate in the range of 1300-1700 K and room temperature for the internal degrees of freedom of the substrate, an efficient nontrapping exploratory search (''helicopter view'') is obtained which visits the correct binding sites. Low energy conformations can then be further investigated by separate search or by dynamic simulated annealing. In both cases the correct minima were identified. The possibility to work with flexible receptors is discussed. (C) 1991 Wiley-Liss, Inc.