title: Research on anti-HIV-1 agents. Investigation on the CD4-Suradista binding mode through docking experiments.
abstract: Sulfonated distamycin (Suradista) derivatives exhibit anti-HIV-1 activity by inhibiting the binding of the viral envelope glycoprotein gp120 to its receptor (CD4). With the aim to propose a possible binding mode between Suradistas and the CD4 macromolecule, molecular docking experiments, followed by energy minimization of the complexes thus obtained, were performed. Computational results show that ligand binding at the CD4 surface involves two or three positively charged regions of the macromolecule, in agreement with the results of X-ray crystallographic analysis of a ternary complex (CD4/gp120/neutralizing antibody) recently reported in the literature. Our findings account well for the structure-activity relationship found for Suradista compounds.
authors.affiliation: Dipartimento Farmaco Chimico Tecnologico, Università degli Studi di Siena, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Manetti
authors.forename: F
authors.initials: F
authors.lastname: Corelli
authors.forename: N
authors.initials: N
authors.lastname: Mongelli
authors.forename: A L
authors.initials: AL
authors.lastname: Borgia
authors.forename: M
authors.initials: M
authors.lastname: Botta
mesh_terms: D019380:Anti-HIV Agents / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D001665:Binding Sites; D015704:CD4 Antigens / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D003198:Computer Simulation; D004214:Distamycins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D015195:Drug Design; D006801:Humans; D066298:In Vitro Techniques; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation
chemical_list: D019380:Anti-HIV Agents; D015704:CD4 Antigens; D004214:Distamycins; D008024:Ligands