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Molecular Dynamics Simulations of Peptide Inhibitors Complexed With Trypanosoma cruzi Trypanothione Reductase
Author(s) -
Da Rocha Pita Samuel Silva,
Batista Paulo Ricardo,
Albuquerque Magaly Girão,
Pascutti Pedro Geraldo
Publication year - 2012
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/j.1747-0285.2012.01429.x
Subject(s) - trypanosoma cruzi , enzyme , peptide , reductase , biochemistry , chagas disease , trypanosoma , molecular dynamics , biology , chemistry , computational biology , genetics , virology , computer science , computational chemistry , parasite hosting , world wide web
The drugs against tropical neglected diseases, especially Chagas’ Disease, were launched more than 30 years ago, and the development of resistance requires the discovery of new and more effective chemotherapeutic agents. Trypanosoma cruzi has a redox enzyme called trypanothione reductase which was successfully inhibited for peptide derivatives (McKie et al. , Amino Acids, 2001, 20: 145). This work aims at studying the mechanism of inhibition of this enzyme through molecular dynamics simulations and evaluating the behavior of some derivatives when inhibiting this protein. We should affirm that any particular molecular dynamics analysis tools (Hbond pattern, 3‐D root‐mean‐square deviation, solvent accessible surface area, etc.) cannot be used apart from the others to justify completely these peptides inhibitory patterns. Based on our results, we reproduced the experimental data and, moreover, we discriminated against a new site in enzyme aperture, which can assist the development of powerful inhibitors against trypanothione reductase enzyme.