title: Investigation on the sucrose binding pocket of HIV-1 Integrase by molecular dynamics and synergy experiments.
abstract: Enzymes whose catalytic activity depends on multimeric assembly are targets for inhibitors that perturb the interactions between the protein subunits such as the HIV-1 Integrase (IN). Sucrose has been recently crystallized in complex with IN revealing an allosteric binding pocket at the monomer-monomer interface. Herein, molecular dynamics were applied to theoretically test the effect of this small ligand on IN. As a result, such a compound increases the mutual free energy of binding between the two interacting monomers. Biological experiments confirmed the computational forecast.
authors.affiliation: Dipartimento Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, via A. Moro, 53100 Siena, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Tintori
authors.affiliation: Department of Life and Environmental Sciences, University of Cagliari, Cittadella Universitaria di Monserrato, Monserrato, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Esposito
authors.affiliation: Dipartimento di Scienze del Farmaco e dei Prodotti per la Salute, Università di Messina, Viale Annunziata, I-98168 Messina, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Morreale
authors.affiliation: Dipartimento Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, via A. Moro, 53100 Siena, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Martini
authors.affiliation: Department of Life and Environmental Sciences, University of Cagliari, Cittadella Universitaria di Monserrato, Monserrato, Italy.
authors.forename: Enzo
authors.initials: E
authors.lastname: Tramontano
authors.affiliation: Dipartimento Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, via A. Moro, 53100 Siena, Italy; Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, College of Science and Technology, Temple University, BioLife Science Bldg., Suite 333, 1900 N 12th Street, Philadelphia, PA 19122, USA. Electronic address: botta.maurizio@gmail.com.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Botta
mesh_terms: D001665:Binding Sites; D004357:Drug Synergism; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology; D019427:HIV Integrase / Q000737:chemistry / Q000378:metabolism*; D019428:HIV Integrase Inhibitors / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology*; D006801:Humans; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D055503:Protein Multimerization / Q000187:drug effects; D000068898:Raltegravir Potassium / Q000494:pharmacology; D013395:Sucrose / Q000494:pharmacology*; D013816:Thermodynamics
chemical_list: D019428:HIV Integrase Inhibitors; D000068898:Raltegravir Potassium; D013395:Sucrose; D019427:HIV Integrase; C514801:p31 integrase protein, Human immunodeficiency virus 1
keywords: HIV-1 Integrase; Molecular dynamics; Protein–protein interaction; Sucrose