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PLoS One. 2016 Feb 9;11(2):e0148974. doi: 10.1371/journal.pone.0148974. eCollection 2016.

Highly Accurate Structure-Based Prediction of HIV-1 Coreceptor Usage Suggests Intermolecular Interactions Driving Tropism.

Author information

1
Artie McFerrin Department of Chemical Engineering, Texas A&M University, College Station, TX, United States of America.
2
Texas A&M Energy Institute, Texas A&M University, College Station, TX, United States of America.
3
Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ, United States of America.

Abstract

HIV-1 entry into host cells is mediated by interactions between the V3-loop of viral glycoprotein gp120 and chemokine receptor CCR5 or CXCR4, collectively known as HIV-1 coreceptors. Accurate genotypic prediction of coreceptor usage is of significant clinical interest and determination of the factors driving tropism has been the focus of extensive study. We have developed a method based on nonlinear support vector machines to elucidate the interacting residue pairs driving coreceptor usage and provide highly accurate coreceptor usage predictions. Our models utilize centroid-centroid interaction energies from computationally derived structures of the V3-loop:coreceptor complexes as primary features, while additional features based on established rules regarding V3-loop sequences are also investigated. We tested our method on 2455 V3-loop sequences of various lengths and subtypes, and produce a median area under the receiver operator curve of 0.977 based on 500 runs of 10-fold cross validation. Our study is the first to elucidate a small set of specific interacting residue pairs between the V3-loop and coreceptors capable of predicting coreceptor usage with high accuracy across major HIV-1 subtypes. The developed method has been implemented as a web tool named CRUSH, CoReceptor USage prediction for HIV-1, which is available at http://ares.tamu.edu/CRUSH/.

PMID:
26859389
PMCID:
PMC4747591
DOI:
10.1371/journal.pone.0148974
[Indexed for MEDLINE]
Free PMC Article

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