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Computational and Mathematical Methods in Medicine
Volume 8, Issue 2, Pages 113-124
Original Article

Docking Simulations and QM/MM Studies between Isoniazid Prodrug, Catalase-Peroxidase (KatG) and S315T Mutant from Mycobacterium tuberculosis

1Departamento de Química, Universidade Federal de Lavras—UFLA, Campus Universitário, Lavras, Caixa Postal 3037, Lavras CEP: 37200-000, MG, Brazil
2Centro Brasileiro de Pesquisas Físicas (CBPF), Rua Dr. Xavier Sigaud, 150, Urca, Rio de janeiro 22290-180, RJ, Brazil
3Departamento de Química Orgânica, Instituto de Química, Universidade Federal do Rio de Janeiro, Ilha do Fundão, CT, Bl. A, Lab. 609, Rio de Janeiro 21949-900, RJ, Brazil
4LEEM Físico-Química, Instituto de Química, Universidade de Brasília—UnB, Cidade Universitária, Campus Darcy Ribeiro, Brasília 70919-970-DF, CEP, Brazil

Received 3 August 2006; Revised 15 February 2007; Accepted 20 February 2007

Copyright © 2007 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Isoniazid (INH), an antibiotic used to treat tuberculosis (TB), is a prodrug requiring activation by the Mycobacterium tuberculosis KatG (mtKatG). In the present work, theoretical calculations were carried out to locate the most energetically-favorable INH–KatG interaction modes using the experimental structure of a wild type and mutant mtKatG active site. The S315T mutation significantly affects the ability of the enzyme to convert INH to isonicotinic acid in vitro. The results showed that significant changes occur in the INH binding pattern when serine is replaced by threonine.