title: Genotype dependent QSAR for HIV-1 protease inhibition.
abstract: The development of drug-resistant viruses limits the therapeutic success of anti-HIV therapies. Some of these genetic HIV-variants display complex mutational patterns in their pol gene that codes for protease and reverse transcriptase, the most investigated molecular targets for antiretroviral therapy. In this paper, we present a computational structure-based approach to predict the resistance of a HIV-1 protease strain to amprenavir by calculating the interaction energy of the drug with HIV-1 protease. By considering the interaction energy per residue, we can identify what residue mutations contribute to drug-resistance. This approach is presented here as a structure-based tool for the prediction of resistance of HIV-1 protease toward amprenavir, with a view to use the drug-protein interaction-energy pattern in a lead-optimization procedure for the discovery of new anti-HIV drugs.
authors.affiliation: Tibotec BVBA, Gen. De Wittelaan L11 B3, B-2800 Mechelen, Belgium. cboutton@tibbe.jnj.com
authors.forename: Carlo W
authors.initials: CW
authors.lastname: Boutton
authors.forename: Hendrik L
authors.initials: HL
authors.lastname: De Bondt
authors.forename: Marc R
authors.initials: MR
authors.lastname: De Jonge
mesh_terms: D002219:Carbamates; D024882:Drug Resistance, Viral; D005663:Furans; D005838:Genotype; D016333:HIV Protease / Q000737:chemistry* / Q000235:genetics*; D017320:HIV Protease Inhibitors / Q000737:chemistry*; D015497:HIV-1 / Q000187:drug effects; D009154:Mutation; D021281:Quantitative Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology; D013816:Thermodynamics
chemical_list: D002219:Carbamates; D005663:Furans; D017320:HIV Protease Inhibitors; D013449:Sulfonamides; C095108:amprenavir; D016333:HIV Protease