Effect of ligand binding on the dynamics of trypsin. Comparison of different approaches
Effect of ligand binding on the dynamics of trypsin. Comparison of different approaches
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DOI：
10.1016/j.jmgm.2014.02.001
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发表时间：
2014-04-01
影响因子：
2.9
通讯作者：
Kurbanov, Rauf
中科院分区：
文献类型：
--
作者：
Ermakova, Elena;Kurbanov, Rauf
通过分子动力学模拟研究了配体与胰蛋白酶结合诱导的分子内信号转导。配体结合改变残基-残基相互作用能量并抑制与配体直接接触的环的迁移率。这些环的移动性降低导致附近环的灵活性改变，从而将信息从配体结合位点传输到远程位点。对所有残基的灵活性的分析证实了环L1(185-188)和L2(221-224)与活性中心中的残基之间的偶联。通过动力学网络和协方差矩阵分析证实了 S1 口袋残基对于从活性中心到底物结合位点的信号转导的重要性。高斯网络模型和主成分分析表明，活性中心残基在最慢的波动中具有零振幅，充当铰链或锚点。总的来说，我们的结果为蛋白质-配体相互作用提供了新的见解，并显示了变构信号如何发生。 (C) 2014 Elsevier Inc. 保留所有权利。
The intramolecular signal transduction induced by the binding of ligands to trypsin was investigated by molecular dynamics simulations. Ligand binding changes the residue-residue interaction energies and suppresses the mobility of loops that are in direct contact with the ligand. The reduced mobility of these loops results in the altered flexibility of the nearby loops and thereby transmits the information from ligand binding site to the remote sites. The analysis of the flexibility of all residues confirmed the coupling between loops Ll (185-188) and L2 (221-224) and the residues in the active center. The significance of S1 pocket residues for the signal transduction from the active center to the substratebinding site was confirmed by the dynamical network and covariance matrix analyses. Gaussian network model and principal component analysis demonstrated that the active center residues had zero amplitude in the slowest fluctuations acting as hinges or anchors. Overall, our results provide a new insight into protein-ligand interactions and show how the allosteric signaling may occur. (C) 2014 Elsevier Inc. All rights reserved.