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Specific interactions and binding free energies between thermolysin and dipeptides: Molecular simulations combined with Ab initio molecular orbital and classical vibrational analysis
Author(s) -
Dedachi Kenichi,
Hirakawa Tatsuya,
Fujita Seiya,
Khan Mahmud Tareq Hassan,
Sylte Ingebrigt,
Kurita Noriyuki
Publication year - 2011
Publication title -
journal of computational chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.907
H-Index - 188
eISSN - 1096-987X
pISSN - 0192-8651
DOI - 10.1002/jcc.21887
Subject(s) - thermolysin , fragment molecular orbital , chemistry , dipeptide , ab initio , molecule , molecular dynamics , molecular orbital , computational chemistry , binding energy , peptide , stereochemistry , biochemistry , enzyme , organic chemistry , atomic physics , physics , trypsin
Thermolysin (TLN) is a metalloprotease widely used as a nonspecific protease for sequencing peptide and synthesizing many useful chemical compounds by the chemical industry. It was experimentally shown that the activity and functions of TLN are inhibited by the binding of many types of amino acid dipeptides. However, the binding mechanisms between TLN and dipeptides have not been clarified at the atomic and electronic levels. In this study, we investigated the binding mechanisms between TLN and four dipeptides. Specific interactions and binding free energies (BFEs) between TLN and the dipeptides were calculated using molecular simulations based on classical molecular dynamics and ab initio fragment molecular orbital (FMO) methods. The molecular systems were embedded in solvating water molecules during calculations. The calculated BFEs were qualitatively consistent with the trend of the experimentally observed inhibition of TLN activity by binding of the dipeptides. In addition, the specific interactions between the dipeptides and each amino acid residue of TLN or solvating water molecules were elucidated by the FMO calculations. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011