氢键和极性相互作用在抑制剂-蛋白结合专一性识别过程中起到重要作用。抑制剂Benzamidine ( BEN)与胰岛素trypsin相互作用机制的阐明有助于胰岛素高效抑制剂的研发。本文采用分子动力学模拟和MM-PBSA( molecular mechanics-Poisson Boltzmann surface area)从原子层次上研究BEN与胰岛素的结合模式。结果表明抑制剂BEN的脒基不仅与 Asp189的羰基产生静电相互作用,而且与残基 Ser190和Gly214形成氢键相互作用。基于残基能量分解的计算表明抑制剂的苯基与残基His58, Cys191, Gln192, Trp211, Gly212和Cys215形成有利于抑制剂结合的疏水性相互作用。期望当前的研究能为胰岛素有效抑制剂的研发提供重要的理论指导。%Hydrogen bonding and polar interactions play important part in identification of binding specificity of inhibitors to proteins. Clarification of interaction mechanism of inhibitor benzamidine ( BEN ) with trypsin is helpful for designs of potent inhibitors targeting trypsin. In the present work, molecular dynamics simulations and molecular mechanics-Poisson Boltzmann surface area ( MM-PBSA ) were adopted to study binding mode of BEN to trypsin at atomic level. The results show that the amidinium group of BEN not only produces favorable e-lectrostatic interactions with residue Asp189 , but also form hydrogen bonding interactions with residues Ser190 and Gly214. Calculations of residue-based energy decomposition suggest that the hydrophobic phenyl of BEN generates favorable van der Waals interactions with residues His58 , Cys191 , Gln192 , Trp211 , Gly212 and Cys215. This study was expected to provide significant theoretical guidance for designs of potent inhibitors targe-ting trypsin.
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