徳島大学 教育・研究者情報データベース(EDB)

1. 吉田 達貞

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2. (英) Hitaoka, Seiji

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3. (英) Mashima, Akira

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4. (英) Sugimoto, Takuya

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5. (英) Matoba, Hiroshi

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6. 中馬 寛

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(英) 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)

(英) 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.

1. (英) Article.Affiliation: Institute of Health Biosciences, The University of Tokushima Graduate School , 1-78 Shomachi, Tokushima 770-8505, Japan.

2. (英) Article.PublicationTypeList.PublicationType: JOURNAL ARTICLE