Correlation Analyses on Binding Affinity of Substituted Benzenesulfonamides with Carbonic Anhydrase Using ab Initio MO Calculations on Their Complex Structures

Abstract

Quantitative structure-activity relationship analyses on the free energy change during complex formation between substituted benzenesulfonamides (BSAs) and bovine carbonic anhydrase II (bCA II) were performed using generilized Born/surface area (GB/SA) and ab initio fragment molecular orbital (FMO) calculations for the whole complex structures. The result shows that the overall free energy change is governed by the contribution from solvation and dissociation free energy changes accompanying by complex formation. The FMO-IFIE (interfragment interaction energy) analysis quantitatively revealed that the intrinsic interaction energy of bCA II with BSAs is mostly from interactions with amino acid residues in the active site of bCA II. The "Zn block" (Zn(2+) and three histidine residues coordinated to Zn(2+)) in the active site shows the lowest interaction energy and the greatest variance of interaction energy with BSAs through their coordination interaction. The proposed procedure was demonstrated to provide a quantitative basis for understanding a ligand-protein interaction at electronic and atomic levels.

Fragmentation Methods: A Route to Accurate Calculations on Large Systems

“…Fischer et al 555 improved the scoring functions representing the binding energy for human estrogen receptor subtype R and human retinoic acid receptor of isotype γ, using atomic charges from FMO calculations at the RHF/STO-3G level and concluded that such quantum scoring functions (QSF) describe the electrostatics accurately, and that QSF performs better than force field analogues. Yoshida et al 556 applied FMO/RHF/6-31G to QSAR studies of the binding affinity of substituted benzenesulfonamides with carbonic anhydrase, noting the difficulties in modeling Zn 2+ -containing systems. Hitaoka et al 557 used FMO/ MP2/6-31G in QSAR studies of the binding affinity of sialic acid analogues with influenza virus neuraminidase-1, where they divided the protein into three binding pockets and used the sums of PIEs for these subsystems as separate descriptors.…”

Revisiting the Hansch–Fujita approach and development of a fundamental QSAR

“…We previously proposed a novel QSAR procedure called linear expression by representative energy terms (LERE)-QSAR [17][18][19][20][21] involving molecular calculations such as an ab initio fragment molecular orbital (FMO) one.…”

Docking, CoMFA and CoMSIA studies of a series of sulfonamides derivatives as carbonic anhydrase I inhibitors

“…The X-ray structures of CAs have shown that the zinc ion (Zn +2 ) within the active site is coordinated to three histidine residues and one water molecule (or hydroxide anion) and that the water molecule is replaced by a CA inhibitor as the fourth ligand of Zn +2 . 8 One of the most prominent classes of CA inhibitors is aromatic/heterocyclic sulfonamides which have been studied for the development of antiglaucoma, antitumor, antiobesity or anticonvulsant drugs 9 . Quantitative structure-activity relationship (QSAR) studies generally perform a vital role in drug discovery and design as ligand-based approaches 10 .…”