Journal article
All-atom models of the membrane-spanning domain of HIV-1 gp41 from metadynamics
Biophysical journal, v 99(10), pp 3438-3444
17 Nov 2010
PMID: 21081093
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The 27-residue membrane-spanning domain (MSD) of the HIV-1 glycoprotein gp41 bears conserved sequence elements crucial to the biological function of the virus, in particular a conserved GXXXG motif and a midspan arginine. However, structure-based explanations for the roles of these and other MSD features remain unclear. Using molecular dynamics and metadynamics calculations of an all-atom, explicit solvent, and membrane-anchored model, we study the conformational variability of the HIV-1 gp41 MSD. We find that the MSD peptide assumes a stable tilted α-helical conformation in the membrane. However, when the side chain of the midspan Arg (694) "snorkels" to the outer leaflet of the viral membrane, the MSD assumes a metastable conformation where the highly-conserved N-terminal core (between Lys(681) and Arg(694) and containing the GXXXG motif) unfolds. In contrast, when the Arg(694) side chain snorkels to the inner leaflet, the MSD peptide assumes a metastable conformation consistent with experimental observations where the peptide kinks at Phe(697) to facilitate Arg(694) snorkeling. Both of these models suggest specific ways that gp41 may destabilize viral membrane, priming the virus for fusion with a target cell.
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Details
- Title
- All-atom models of the membrane-spanning domain of HIV-1 gp41 from metadynamics
- Creators
- Vamshi K Gangupomu - Department of Chemical and Biological Engineering, Drexel University, Philadelphia, PA, USACameron F Abrams
- Publication Details
- Biophysical journal, v 99(10), pp 3438-3444
- Publisher
- Elsevier; United States
- Grant note
- R01 AI-084117-01 / NIAID NIH HHS R01 AI084117 / NIAID NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Chemical and Biological Engineering
- Web of Science ID
- WOS:000284438700039
- Scopus ID
- 2-s2.0-78549260745
- Other Identifier
- 991014878124704721
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- Web of Science research areas
- Biophysics