Drug design: New inhibitors for HIV-1 protease based on Nelfinavir as lead

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

Authors

Perez, MAS (Author) Other; Fernandes, PA (Author) FCUP; Ramos, MJ (Author) FCUP

Journal

Title: Journal of Molecular Graphics and Modelling

Vol. 26

Pages: 634-642

ISSN: 1093-3263

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 8 Citations

Scopus - 11 Citations

Scientific classification

FOS: Natural sciences > Computer and information sciences

Other information

Authenticus ID: P-004-77Z

DOI: 10.1016/j.jmgm.2007.03.009

Abstract (EN): Nelfinavir (Viracept (R)) is a potent, non-peptidic inhibitor of HIV-1 Protease, which has been marketed for the treatment of HIV infected patients. However, HIV- I develops drug-resistance which decreases the affinity of Nelfinavir for the binding pocket of Protease. We present here three new; variants of Nelfinavir, which we have designed with computational tools, with greater affinity for HIV-1 Protease than Nelfinavir itself. Accordingly. we have introduced rational modifications in Nelfinavir, optimizing its affinity to the most conserved amino acids in Protease, in order to increase the efficiency of the three new inhibitors. Minimization and molecular dynamics simulations have been carried out on four complexes, HIV-1 Protease with Nelfinavir and subsequently with the new inhibitors, respectively. in order to analyze the behavior of the systems. Additionally. we have calculated the binding free energy differences Protease: inhibitor, which gave us a quantitative idea of the new molecules inhibitory efficiency in silico.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 9