Research on anti-HIV-1 agents. Investigation on the CD4-Suradista binding mode through docking experiments

Sulfonated distamycin (Suradista) derivatives exhibit anti-HIV-1 activity b y inhibiting the binding of the viral envelope glycoprotein gp120 to its re ceptor (CD4). With the aim to propose a possible binding mode between Surad istas and the CD4 macromolecule, molecular docking experiments, followed by energy minimization of the complexes thus obtained, were performed. Comput ational results show that ligand binding at the CD4 surface involves two or three positively charged regions of the macromolecule, in agreement with t he results of X-ray crystallographic analysis of a ternary complex (CD4/gp1 20/neutralizing antibody) recently reported in the literature. Our findings account well for the structure-activity relationship found for Suradista c ompounds.