title: Integrative computational protocol for the discovery of inhibitors of the Helicobacter pylori nickel response regulator (NikR).
abstract: In order to identify novel inhibitors of the Helicobacter pylori nickel response regulator (HpNikR) an integrative protocol was performed for half a million compounds retrieved from the ZINC database. We firstly implement a structure-based virtual screening to build a library of potential inhibitors against the HpNikR using a docking analysis (AutoDock Vina). The library was then used to perform a hierarchical clustering of docking poses, based on protein-contact footprints calculation from the multiple conformations given by the AutoDock Vina software, and the drug-protein interaction analyses to identify and remove potential promiscuous compounds likely interacting with human proteins, hence causing drug side effects. 250 drug-like compounds were finally proposed as non-promicuous potential inhibitors for HpNikR. These compounds target the DNA-binding sites of HpNikR so that HpNikR-compound binding could be able to mimic key interactions in the DNA-protein recognition process. HpNikR inhibitors with promising potential against H. pylori could also act against other human bacterial pathogens due to the conservation of targeting motif of NikR involved in DNA-protein interaction.
authors.affiliation: Laboratorio de Bioinformática, Centro de Biotecnología Genómica, Instituto Politécnico Nacional, Boulevard del Maestro esquina Elías Piña, Colonia Narciso Mendoza, 88710 Ciudad Reynosa, Tamaulipas, Mexico. asegurac@ipn.mx
authors.forename: Aldo
authors.initials: A
authors.lastname: Segura-Cabrera
authors.forename: Xianwu
authors.initials: X
authors.lastname: Guo
authors.forename: Arturo
authors.initials: A
authors.lastname: Rojo-Domínguez
authors.forename: Mario A
authors.initials: MA
authors.lastname: Rodríguez-Pérez
mesh_terms: D020816:Amino Acid Motifs; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D003198:Computer Simulation; D004269:DNA, Bacterial / Q000737:chemistry / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D016208:Databases, Factual; D055808:Drug Discovery / Q000379:methods*; D016481:Helicobacter Infections / Q000188:drug therapy* / Q000382:microbiology; D016480:Helicobacter pylori / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009532:Nickel / Q000378:metabolism; D011485:Protein Binding / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000235:genetics; D012097:Repressor Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D012235:Rhodamines / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D054852:Small Molecule Libraries / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D013045:Species Specificity; D013329:Structure-Activity Relationship
chemical_list: D001426:Bacterial Proteins; D004269:DNA, Bacterial; D004268:DNA-Binding Proteins; C523724:NikR protein, Helicobacter pylori; D012097:Repressor Proteins; D012235:Rhodamines; D054852:Small Molecule Libraries; D009532:Nickel