Inference of Epistatic Effects Leading to Entrenchment and Drug Resistance in HIV-1 Protease.

ABSTRACT: Understanding the complex mutation patterns that give rise to drug resistant viral strains provides a foundation for developing more effective treatment strategies for HIV/AIDS. Multiple sequence alignments of drug-experienced HIV-1 protease sequences contain networks of many pair correlations which can be used to build a (Potts) Hamiltonian model of these mutation patterns. Using this Hamiltonian model, we translate HIV-1 protease sequence covariation data into quantitative predictions for the probability of observing specific mutation patterns which are in agreement with the observed sequence statistics. We find that the statistical energies of the Potts model are correlated with the fitness of individual proteins containing therapy-associated mutations as estimated by in vitro measureme

SUBMITTER: Flynn WF 

PROVIDER: S-EPMC5435099 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature