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Published on: December 1, 2011
A hierarchical model of HIV-1 protease drug resistance
1Department of Molecular Biology, The Scripps Research Institute, La Jolla, California, USA. goodsell@scipps.edu
Abstract:
A hierarchical model of HIV-1 drug therapy may be used to evaluate new inhibitors and test new treatment strategies that address the problem of drug resistance. The model includes an atomic representation of drug-protease interaction, evaluation of viral fitness based on cleavage of polyprotein substrates during viral maturation, evolutionary modelling of drug resistance mutations in the face of selection pressures by drug and a mathematical description of viral population dynamics in infected individuals. These techniques have been used for the design of resistance-evading inhibitors by computational coevolution techniques and for the optimisation of existing protease inhibitors for improving their robustness in the face of resistance mutation.
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