title: Unconventional plasticity of HIV-1 reverse transcriptase: how inhibitors could open a connection "gate" between allosteric and catalytic sites.
abstract: Targeted molecular dynamics (TMD) simulations allowed for identifying the chemical/structural features of the nucleotide-competitive HIV-1 inhibitor DAVP-1, which is responsible for the disruption of the T-shape motif between Try183 and Trp229 of the reverse transcriptase (RT). DAVP-1 promoted the opening of a connection "gate" between allosteric and catalytic sites of HIV-1 RT, thus explaining its peculiar mechanism of action and providing useful insights to develop novel nucleotide-competitive RT inhibitors.
authors.affiliation: Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena , Via Aldo Moro 2, 53100 Siena, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Bellucci
authors.forename: Lucilla
authors.initials: L
authors.lastname: Angeli
authors.forename: Andrea
authors.initials: A
authors.lastname: Tafi
authors.forename: Marco
authors.initials: M
authors.lastname: Radi
authors.forename: Maurizio
authors.initials: M
authors.lastname: Botta
mesh_terms: D000495:Allosteric Site; D001667:Binding, Competitive; D020134:Catalytic Domain; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors / Q000737:chemistry*; D015497:HIV-1 / Q000737:chemistry* / Q000201:enzymology; D006575:Heterocyclic Compounds, 3-Ring / Q000737:chemistry; D006801:Humans; D007211:Indoles / Q000737:chemistry; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D009570:Nitriles / Q000737:chemistry; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011728:Pyridones / Q000737:chemistry; D011743:Pyrimidines / Q000737:chemistry*; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014753:Vinyl Compounds / Q000737:chemistry*
chemical_list: C550503:4-dimethylamino-6-vinylpyrimidine; C517167:5-methyl-1-(4-nitrophenyl)-2-oxo-2,5-dihydro-1H-pyrido(3,2-b)indole-3-carbonitrile; D006575:Heterocyclic Compounds, 3-Ring; D007211:Indoles; D009570:Nitriles; D011728:Pyridones; D011743:Pyrimidines; D018894:Reverse Transcriptase Inhibitors; C550501:VRX-329747; D014753:Vinyl Compounds; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase