title: 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).
abstract: 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.
authors: Institute of Health Biosciences, The University of Tokushima Graduate School , 1-78 Shomachi, Tokushima 770-8505, Japan.
authors: Tatsusada
authors: T
authors: Yoshida
authors: Seiji
authors: S
authors: Hitaoka
authors: Akira
authors: A
authors: Mashima
authors: Takuya
authors: T
authors: Sugimoto
authors: Hiroshi
authors: H
authors: Matoba
authors: Hiroshi
authors: H
authors: Chuman
mesh_terms: D020780:Matrix Metalloproteinase 9 / Q000737:chemistry*; D008958:Models, Molecular; D015394:Molecular Structure; D021281:Quantitative Structure-Activity Relationship; D011789:Quantum Theory; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry*
chemical_list: D013449:Sulfonamides; D020780:Matrix Metalloproteinase 9