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| - An ab Initio Investigation of the Interactions Involving the Aromatic Group of the Set ofFluorinated N-(4-Sulfamylbenzoyl)benzylamine Inhibitors and Human CarbonicAnhydrase II
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| - In this work we investigate the interactions that occur between the aromatic portion of the set of fluorinatedN-(4-sulfamylbenzoyl)benzylamine (SBB) inhibitors and two residues of Human Carbonic Anhydrase II(HCAII), namely Phe-131 and Pro-202. Calculations were carried out at the MP2/aug-cc-pVDZ level of theoryand the counterpoise scheme of Boys and Bernardi was employed to account for the basis set superpositionerror. The most striking result obtained here is that the SBB phenyl ring interacts at least as strongly with theproline pyrrolidine ring as with the phenylalanine phenyl ring, which is surprising because aromatic−aromaticinteractions have long been thought to be particularly favorable in protein and protein−ligand structure.Comparison of the MP2 binding energies to those obtained with the Hartree−Fock method indicates that theattraction between the proline pyrrolidine ring and the SBB phenyl ring is largely attributable to dispersionforces. These favorable interactions between pyrrolidine and phenyl rings may have important implicationsin protein structure because there is potential for proline residues to interact with phenylalanine residues ina fashion analogous to that seen here. A preliminary protein data bank search indicates that the proline−phenylalanine contacts are about 40% as common as those between two phenylalanines. It is also found herethat the number and pattern of fluorine substituents on the SBB phenyl ring is much less important indetermining the SBB−HCAII binding energy than the relative geometric configuration of the interactingpairs.
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