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

• Type: Article in International Scientific Journal
• Date: 2007

Authors

Alexandra T P Carvalho (Author) Other; Pedro A Fernandes (Author) FCUP; Maria J Ramos (Author) FCUP

Journal

Title: International Journal of Quantum Chemistry

Vol. 107

Pages: 292-298

ISSN: 0020-7608

Publisher: Wiley-Blackwell

Indexing

ISI Web of Knowledge - 7 Citations

Scopus - 7 Citations

Scientific classification

FOS: Natural sciences > Chemical sciences

Other information

Authenticus ID: 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 7