Parameterization of AZT - A widely used nucleoside inhibitor of HIV-1 reverse transcriptase

• Tipo: Artigo em Revista Científica Internacional
• Data: 2007

Autores

Alexandra T P Carvalho (Autor) Outra; Pedro A Fernandes (Autor) FCUP; Maria J Ramos (Autor) FCUP

Revista

Título: International Journal of Quantum Chemistry

Vol. 107

Páginas: 292-298

ISSN: 0020-7608

Editora: Wiley-Blackwell

Indexação

ISI Web of Knowledge - 7 Citações

Scopus - 7 Citações

Classificação Científica

FOS: Ciências exactas e naturais > Química

Outras Informações

ID Authenticus: P-004-C0W

DOI: 10.1002/qua.21192

Abstract (EN): Seven nucleoside reverse transcriptase (RT) inhibitors are currently used in the clinical treatment of acquired immunodeficiency syndrome (AIDS). These substrate analogues block DNA synthesis by the viral enzyme RT. However, the emergence of resistant variants of RT allied to their long-term toxicity requires the design of new and better RT inhibitors, with long-term in vivo efficacy. In this work we used density functional theory (DFT) calculations to develop a set of molecular mechanics (MM) parameters committed to the AMBER force field for one of the most used in the clinic nucleoside reverse transcriptase inhibitors (NRTIs): zidovudine (AZT). These parameters were tested by comparing the optimized geometries of AZT at both the DFT and MM levels of theory. The ability of the new parameters to reproduce the torsional energy of the azide group was also verified by scanning the surface in MM with the new parameters and comparing the results with the same potential energy surface (PES) at the DFT level. Finally, the parameters were validated through classical MD simulations of AZT in aqueous environment. (c) 2006 Wiley Periodicals, Inc.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 7