A Combined QM/MM (ONIOM) and QSAR Approach to the Study of Complex Formation of Matrix Metalloproteinase-9 with a Series of Biphenylsulfonamides - LERE-QSAR Analysis (V)
A Combined QM/MM (ONIOM) and QSAR Approach to the Study of Complex Formation of Matrix Metalloproteinase-9 with a Series of Biphenylsulfonamides - LERE-QSAR Analysis (V)
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结合 QM/MM (ONIOM) 和 QSAR 方法研究基质金属蛋白酶 9 与一系列联苯磺酰胺的复合物形成 - LERE-QSAR 分析 (V)
DOI：
10.1021/jp305476x
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发表时间：
2012
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影响因子：
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et al.
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作者：
Yoshida T;et al.
我们以前提出了一种新的定量构效关系（QSAR）的程序称为莱雷（代表性能量项的线性表达式）-QSAR涉及分子计算，如从头计算片段分子轨道的。在本工作中，我们应用LERE-QSAR基质金属蛋白酶-9（MMP-9）与一系列取代联苯磺酰胺类化合物的复合物的形成。结果表明，伴随复合物形成的总体自由能变化主要是由于MMP-9活性位点中与锌原子的静电相互作用的贡献。碳酸酐酶（CA）属于含锌蛋白酶家族。与MMP-9的当前情况相反，CA与一系列苯磺酰胺形成复合物期间的总体自由能变化是由于溶剂化和解离自由能变化的贡献，如先前所报道的。两组结果的比较表明，在两个数据集之间的整体自由能变化的自由能成分的相对贡献的定量差异，对应于那些在各自的经典QSAR方程。的LERE-QSAR程序被证明，定量揭示两种情况下，涉及类似的，但不同的含锌蛋白质在电子和原子水平上的结合机制之间的差异。
We previously proposed a novel QSAR (quantitative structure–activity relationship) procedure called LERE (linear expression by representative energy terms)-QSAR involving molecular calculations such as an ab initio fragment molecular orbital ones. In the present work, we applied LERE-QSAR to complex formation of matrix metalloproteinase-9 (MMP-9) with a series of substituted biphenylsulfonamides. The results shows that the overall free-energy change accompanying complex formation is due to predominantly the contribution from the electrostatic interaction with the zinc atom in the active site of MMP-9. Carbonic anhydrase (CA) belongs to the zinc-containing protease family. In contrast to the current case of MMP-9, the overall free-energy change during complex formation of CA with a series of benzenesulfonamides is due to the contributions from the solvation and dissociation free-energy changes, as previously reported. Comparison of the two sets of results indicates quantitative differences in the relative contributions of free-energy components to the overall free-energy change between the two data sets, corresponding with those in the respective classical QSAR equations. The LERE-QSAR procedure was demonstrated to quantitatively reveal differences in the binding mechanisms between the two cases involving similar but different zinc-containing proteins at the electronic and atomic levels.