title: Collecting and assessing human lactate dehydrogenase-A conformations for structure-based virtual screening.
abstract: Human lactate dehydrogenase-A (LDHA) is emerging as a promising anticancer target. Up to now, structure-based investigations for identifying inhibitors of this enzyme have not explicitly accounted for active site flexibility. In the present study, by combining replica exchange molecular dynamics with network and cluster analyses, we identified reliable LDHA conformations for structure-based ligand design. The selected conformations were challenged and validated by retrospective virtual screening simulations.
authors.affiliation: Department of Pharmacy and Biotechnology, Alma Mater Studiorum-Università di Bologna , via Belmeloro 6, 40126 Bologna, Italy.
authors.forename: Rosa
authors.initials: R
authors.lastname: Buonfiglio
authors.forename: Mariarosaria
authors.initials: M
authors.lastname: Ferraro
authors.forename: Federico
authors.initials: F
authors.lastname: Falchi
authors.forename: Andrea
authors.initials: A
authors.lastname: Cavalli
authors.forename: Matteo
authors.initials: M
authors.lastname: Masetti
authors.forename: Maurizio
authors.initials: M
authors.lastname: Recanatini
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry*; D020134:Catalytic Domain; D016000:Cluster Analysis; D018360:Crystallography, X-Ray; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry*; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000737:chemistry; D007770:L-Lactate Dehydrogenase / Q000037:antagonists & inhibitors / Q000737:chemistry*; D000080864:Lactate Dehydrogenase 5; D008024:Ligands; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D011487:Protein Conformation; D012372:ROC Curve; D014584:User-Computer Interface
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D008024:Ligands; D007770:L-Lactate Dehydrogenase; D000080864:Lactate Dehydrogenase 5