Work

Drug Pressure Selected Mutations in HIV-1 Protease Alter Flap Conformations

Year: 2008

Type: article

Abstract: The flap conformations of two drug-resistant HIV-1 protease constructs were characterized by molecular dynamic (MD) simulations and distance measurements with pulsed electron paramagnetic resonance (EPR) spectroscopy. MD simulations accurately regenerate the experimentally determined distance profiles and provide structural interpretations of the EPR data. The combined analyses show that the average conformation of the flaps, the range of flap opening and closing, and the flexibility of the flaps differ markedly in HIV-1PR as multiple mutations arise in response to antiviral therapy, providing structural insights into the mechanism of inhibitor resistance.

Source: Journal of the American Chemical Society

DOI: 10.1021/ja807531v

Authors: Luis Galiano, Fangyu Ding, Angelo M. Veloro, Mandy E. Blackburn, Carlos Simmerling, Gail E. Fanucci

Institutions: University of Florida, Stony Brook School, Stony Brook University

Language: English

Topic: Protein Structure and Dynamics

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: green

Funders: U.S. Department of Energy, National Centre for Supercomputing Applications, Academy of Finland, National Institute of General Medical Sciences

Awards: G1672422240, Computational Studies of Model Systems for Protein Unfolded States