Molecular dynamics model of unliganded HIV-1 reverse transcriptase

• Type: Article in International Scientific Journal
• Date: 2006

Authors

Carvalho, ATP (Author) Other; Fernandes, PA (Author) FCUP; Ramos, MJ (Author) FCUP

Journal

Title: Medicinal Chemistry

Vol. 2

Pages: 491-498

ISSN: 1573-4064

Publisher: Bentham Science

Indexing

ISI Web of Knowledge

Scopus - 4 Citations

Other information

Authenticus ID: P-007-G5Y

DOI: 10.2174/157340606778250270

Abstract (EN): HIV-1 RT is one of the most important antiviral targets in the treatment of acquired immunodeficiency syndrome (AIDS). Several crystallographic structures are available for this enzyme, mostly with bound inhibitors. Despite their importance for structure based drug design towards new anti-HIV retrovirals, the X-ray structures of the unliganded enzyme could only be obtained incomplete, with a low resolution and until recently even the conformation of the p66 thumb was controversial. In this work we have aligned different X-ray RT structures, and built up a computational model of RT using homology modeling, which was afterwards refined and validated through MD simulations with explicit solvent. The model enzyme was structurally stable through the whole MD simulation, showing a RMSD of 2 Å from the starting geometry. The Ramanchandram plot has improved along the simulation. Both intra-domain and interdomain movements were observed. The thumb kept its closed conformation through the whole simulation. A contact map, hydration sites study and a detailed analysis of the solvation of the nucleotide binding site are also presented. © 2006 Bentham Science Publishers Ltd.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 8