title: Calculation of binding energy using BLYP/MM for the HIV-1 integrase complexed with the S-1360 and two analogues.
abstract: Integrase (IN) is one of the three human immunodeficiency virus type 1 (HIV-1) enzymes essential for effective viral replication. S-1360 is a potent and selective inhibitor of HIV-1 IN. In this work, we have carried out molecular dynamics (MD) simulations using a hybrid Quantum Mechanics/Molecular Mechanics (QM/MM) approach, to determine the protein-ligand interaction energy for S-1360 and two analogues. Analysis of the MD trajectories reveals that the strongest protein-inhibitor interactions, observed in the three studied complexes, are established with Lys-159 residue and Mg(2+) cation. Calculations of binding energy using BLYP/MM level of theory reveal that there is a direct relationship between this theoretical computed property and the experimental determined anti-HIV activity.
authors.affiliation: Departamento de Química, Centro de Ciências Exatas e Naturais, Universidade Federal do Pará, CP 11101, 66075-110 Belém, PA, Brazil. nahum@ufpa.br
authors.forename: Cláudio N
authors.initials: CN
authors.lastname: Alves
authors.forename: Sergio
authors.initials: S
authors.lastname: Martí
authors.forename: Raquel
authors.initials: R
authors.lastname: Castillo
authors.forename: Juan
authors.initials: J
authors.lastname: Andrés
authors.forename: Vicent
authors.initials: V
authors.lastname: Moliner
authors.forename: Iñaki
authors.initials: I
authors.lastname: Tuñón
authors.forename: Estanislao
authors.initials: E
authors.lastname: Silla
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D018360:Crystallography, X-Ray; D005663:Furans / Q000737:chemistry*; D019427:HIV Integrase / Q000737:chemistry*; D019428:HIV Integrase Inhibitors / Q000737:chemistry*; D006801:Humans; D008239:Lysine / Q000737:chemistry; D008274:Magnesium / Q000737:chemistry; D008956:Models, Chemical; D011407:Propane / Q000031:analogs & derivatives* / Q000737:chemistry; D011487:Protein Conformation; D011758:Pyrroles / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000737:chemistry*
chemical_list: C521395:1-(5-((4-fluorophenyl)methyl)pyrrol-2-yl)-3-hydroxy-3-(2H-1,2,4-triazol-3-yl)prop-2-en-1-one; D005663:Furans; D019428:HIV Integrase Inhibitors; D011758:Pyrroles; C451733:S 1360; D014230:Triazoles; D019427:HIV Integrase; D008274:Magnesium; D008239:Lysine; D011407:Propane