title: Modified solvent accessibility free energy prediction analysis of cyclic urea inhibitors binding to the HIV-1 protease.
abstract: One of the most successful drug targets against AIDS in the last decade has been the HIV-1 protease (HIV-1 PR), an enzyme that processes the polyprotein gene products into active replicative viral proteins. In our quest for a wide-ranging, binding free energy function we have extended the solvent accessibility free energy predictor (SAFE_p) method, recently developed for peptidic HIV-1 PR inhibitors, to the study of the binding of cyclic urea (CU) HIV-1 PR inhibitors. Our results show that there is a need for a specific term depicting polar contacts to be added to the original SAFE_p analytical expression, an outcome not seen in our studies of HIV-1 PR peptidic inhibitors. Nevertheless, despite the higher profile of the electrostatic interactions in the binding of the CU inhibitors, our analysis indicates that CU inhibitor binding is still driven by the hydrophobic entropic contribution, as much as for the peptidic inhibitors.
authors.affiliation: Departamento de Química Orgánica, Facultad de Química, Universidad de Santiago de Compostela, 15782 Santiago de Compostela, Spain. fsussman@usc.es
authors.forename: Fredy
authors.initials: F
authors.lastname: Sussman
authors.forename: M Carmen
authors.initials: MC
authors.lastname: Villaverde
authors.forename: Luis
authors.initials: L
authors.lastname: Martínez
mesh_terms: D001665:Binding Sites; D015658:HIV Infections / Q000188:drug therapy; D016333:HIV Protease / Q000737:chemistry / Q000378:metabolism; D017320:HIV Protease Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular; D015202:Protein Engineering; D012997:Solvents; D055672:Static Electricity; D013816:Thermodynamics; D014508:Urea / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology
chemical_list: D017320:HIV Protease Inhibitors; D012997:Solvents; D014508:Urea; D016333:HIV Protease