Next Article in Journal / Special Issue
Making a Short Story Long: Regulation of P-TEFb and HIV-1 Transcriptional Elongation in CD4+ T Lymphocytes and Macrophages
Previous Article in Journal / Special Issue
The Surprising Role of Amyloid Fibrils in HIV Infection
Article Menu

Export Article

Open AccessArticle
Biology 2012, 1(1), 81-93; doi:10.3390/biology1010081

Higher Desolvation Energy Reduces Molecular Recognition in Multi-Drug Resistant HIV-1 Protease

1
Department of Biochemistry and Molecular Biology, Wayne State University School of Medicine, Detroit, MI 48201, USA
2
Department of Molecular Pharmacology and Biochemistry, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
*
Author to whom correspondence should be addressed.
Received: 30 April 2012 / Revised: 23 May 2012 / Accepted: 25 May 2012 / Published: 31 May 2012
(This article belongs to the Special Issue Structural and Molecular Biology of HIV)
View Full-Text   |   Download PDF [775 KB, uploaded 1 June 2012]   |  

Abstract

Designing HIV-1 protease inhibitors that overcome drug-resistance is still a challenging task. In this study, four clinical isolates of multi-drug resistant HIV-1 proteases that exhibit resistance to all the US FDA-approved HIV-1 protease inhibitors and also reduce the substrate recognition ability were examined. A multi-drug resistant HIV-1 protease isolate, MDR 769, was co-crystallized with the p2/NC substrate and the mutated CA/p2 substrate, CA/p2 P1’F. Both substrates display different levels of molecular recognition by the wild-type and multi-drug resistant HIV-1 protease. From the crystal structures, only limited differences can be identified between the wild-type and multi-drug resistant protease. Therefore, a wild-type HIV-1 protease and four multi-drug resistant HIV-1 proteases in complex with the two peptides were modeled based on the crystal structures and examined during a 10 ns-molecular dynamics simulation. The simulation results reveal that the multi-drug resistant HIV-1 proteases require higher desolvation energy to form complexes with the peptides. This result suggests that the desolvation of the HIV-1 protease active site is an important step of protease-ligand complex formation as well as drug resistance. Therefore, desolvation energy could be considered as a parameter in the evaluation of future HIV-1 protease inhibitor candidates. View Full-Text
Keywords: multi-drug resistant HIV-1 protease; X-ray crystallography; desolvation energy multi-drug resistant HIV-1 protease; X-ray crystallography; desolvation energy
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Wang, Y.; Dewdney, T.G.; Liu, Z.; Reiter, S.J.; Brunzelle, J.S.; Kovari, I.A.; Kovari, L.C. Higher Desolvation Energy Reduces Molecular Recognition in Multi-Drug Resistant HIV-1 Protease. Biology 2012, 1, 81-93.

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Biology EISSN 2079-7737 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top