title: Inhibitors of HIV-protease from computational design. A history of theory and synthesis still to be fully appreciated.
abstract: Despite the fact that HIV-Protease is an over 20 years old target, computational approaches to rational design of its inhibitors still have a great potential to stimulate the synthesis of new compounds and the discovery of new, potent derivatives, ever capable to overcome the problem of drug resistance. This review deals with successful examples of inhibitors identified by computational approaches, rather than by knowledge-based design. Such methodologies include the development of energy and scoring functions, docking protocols, statistical models, virtual combinatorial chemistry. Computations addressing drug resistance, and the development of related models as the substrate envelope hypothesis are also reviewed. In some cases, the identified structures required the development of synthetic approaches in order to obtain the desired target molecules; several examples are reported.
authors.forename: Federico
authors.initials: F
authors.lastname: Berti
authors.forename: Vladimir
authors.initials: V
authors.lastname: Frecer
authors.affiliation: Department of Chemical and Pharmaceutical Sciences, University of Trieste, via Giorgieri 1, 34127 Trieste, Italy. fberti@units.it.
authors.forename: Stanislav
authors.initials: S
authors.lastname: Miertus
mesh_terms: D020650:Combinatorial Chemistry Techniques; D017076:Computer-Aided Design; D017320:HIV Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry*; D006801:Humans; D008958:Models, Molecular; D021281:Quantitative Structure-Activity Relationship
chemical_list: D017320:HIV Protease Inhibitors