title: A hierarchical model of HIV-1 protease drug resistance.
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.
authors.affiliation: Department of Molecular Biology, The Scripps Research Institute, La Jolla, California, USA. goodsell@scipps.edu
authors.forename: David S
authors.initials: DS
authors.lastname: Goodsell
mesh_terms: D020134:Catalytic Domain / Q000235:genetics; D019295:Computational Biology; D017076:Computer-Aided Design; D019020:Directed Molecular Evolution; D015195:Drug Design; D024882:Drug Resistance, Viral / Q000235:genetics; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology; D016333:HIV Protease / Q000737:chemistry / Q000187:drug effects* / Q000235:genetics; D017320:HIV Protease Inhibitors / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D006801:Humans; D008954:Models, Biological; D008958:Models, Molecular; D009154:Mutation
chemical_list: D017320:HIV Protease Inhibitors; D016333:HIV Protease