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Subtractive sequence analysis aided druggable targets mining in Burkholderia cepacia complex and finding inhibitors through bioinformatics approach.
Hassan, Syed Shah; Shams, Rida; Camps, Ihosvany; Basharat, Zarrin; Sohail, Saman; Khan, Yasmin; Ullah, Asad; Irfan, Muhammad; Ali, Javed; Bilal, Muhammad; Morel, Carlos M.
Afiliação
  • Hassan SS; Jamil-ur-Rehman Center for Genome Research, Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan. hassanchemist83@gmail.com.
  • Shams R; Centre for Technological Development in Health (CDTS), Oswaldo Cruz Foundation (Fiocruz), Building "Expansão", 8th Floor Room 814, Av. Brasil 4036, Manguinhos, Rio de Janeiro, RJ, 21040-361, Brazil. hassanchemist83@gmail.com.
  • Camps I; Department of Chemistry, Islamia College Peshawar, Peshawar, 25000, KP, Pakistan. hassanchemist83@gmail.com.
  • Basharat Z; Department of Chemistry, Islamia College Peshawar, Peshawar, 25000, KP, Pakistan.
  • Sohail S; Laboratório de Modelagem Computacional-LaModel, Instituto de Ciências Exatas-ICEx. Universidade Federal de Alfenas-UNIFAL-MG, Alfenas, Minas Gerais, Brazil.
  • Khan Y; High Performance & Quantum Computing Labs, Waterloo, Canada.
  • Ullah A; Jamil-ur-Rehman Center for Genome Research, Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan.
  • Irfan M; Department of Chemistry, Islamia College Peshawar, Peshawar, 25000, KP, Pakistan.
  • Ali J; Jamil-ur-Rehman Center for Genome Research, Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan.
  • Bilal M; Department of Chemistry, Islamia College Peshawar, Peshawar, 25000, KP, Pakistan.
  • Morel CM; Jamil-ur-Rehman Center for Genome Research, Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan.
Mol Divers ; 27(6): 2823-2847, 2023 Dec.
Article em En | MEDLINE | ID: mdl-36567421
Burkholderia cepacia complex (BCC) is a group of gram-negative bacteria composed of at least 20 different species that cause diseases in plants, animals as well as humans (cystic fibrosis and airway infection). Here, we analyzed the proteomic data of 47 BCC strains by classifying them in three groups. Phylogenetic analyses were performed followed by individual core region identification for each group. Comparative analysis of the three individual core protein fractions resulted in 1766 ortholog/proteins. Non-human homologous proteins from the core region gave 1680 proteins. Essential protein analyses reduced the target list to 37 proteins, which were further compared to a closely related out-group, Burkholderia gladioli ATCC 10,248 strain, resulting in 21 proteins. 3D structure modeling, validation, and druggability step gave six targets that were subjected to further target prioritization parameters which ultimately resulted in two BCC targets. A library of 12,000 ZINC drug-like compounds was screened, where only the top hits were selected for docking orientations. These included ZINC01405842 (against Chorismate synthase aroC) and ZINC06055530 (against Bifunctional N-acetylglucosamine-1-phosphate uridyltransferase/Glucosamine-1-phosphate acetyltransferase glmU). Finally, dynamics simulation (200 ns) was performed for each ligand-receptor complex, followed by ADMET profiling. Of these targets, details of their applicability as drug targets have not yet been elucidated experimentally, hence making our predictions novel and it is suggested that further wet-lab experimentations should be conducted to test the identified BCC targets and ZINC scaffolds to inhibit them.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Complexo Burkholderia cepacia Tipo de estudo: Diagnostic_studies / Prognostic_studies Limite: Animals Idioma: En Revista: Mol Divers Assunto da revista: BIOLOGIA MOLECULAR Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Paquistão

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Complexo Burkholderia cepacia Tipo de estudo: Diagnostic_studies / Prognostic_studies Limite: Animals Idioma: En Revista: Mol Divers Assunto da revista: BIOLOGIA MOLECULAR Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Paquistão