Please use this identifier to cite or link to this item: http://hdl.handle.net/20.500.12779/5834
Title: Molecular Dynamics and DFT Study on HIV-1 Nucleocapsid Protein-7 in Complex with Viral Genome.
Authors: Mori, Mattia 
Dietrich, U
Manetti, Fabrizio 
Botta, Maurizio 
Issue Date: 2010
Project: None 
Journal: JOURNAL OF CHEMICAL INFORMATION AND MODELING
Abstract: 
The HIV-1 nucleocapsid protein-7 (NCp7) is a highly basic, small zinc-binding protein involved in both deoxyribonucleic (DNA) and ribonucleic (RNA) acids annealing and in viral particle maturation including genome encapsidation, with an additional chaperoning activity toward reverse transcriptase by promoting the two obligatory strand transfers during reverse transcription. Because of its interaction with highly conserved sequences of the HIV-1 genome, NCp7 is being considered a new potential drug target, resistant to mutation, for antiviral activity. The high flexibility of this protein has, however, limited the identification of structural determinants involved in the interaction with stranded sequences of DNA and RNA. Here, we provide a quantum mechanics (density functional theory) study of the zinc-binding motifs and a molecular dynamics simulation of the protein in complex with RNA and DNA, starting from available nuclear magnetic resonance (NMR) structures. Results show that the interaction between the NCp7 and the viral genome is probably based on electrostatic interactions due to a cluster of basic residues, which is reinforced by the exploitation of nonelectrostatic contacts that further stabilize the complexes. Moreover, a possible mechanism for DNA destabilization that involves amino acids T24 and R26 is also hypothesized. Finally, a network of hydrophobic and hydrogen-bond interactions for the stabilization of complexes with DNA and, especially, with RNA is described here for the first time. The complexes between NCp7 and both DNA and RNA, resulting from computer simulations, showed structural properties that are in agreement with most of the currently available molecular biology evidence and could be considered as reliable models (better than NMR structures currently available) for subsequent structure-based ligand design approaches.
Description: 
38628
URI: http://hdl.handle.net/20.500.12779/5834
ISSN: 1549-9596
DOI: 10.1021/ci100070m
Appears in Collections:Publications

Show full item record

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.