title: A user-friendly web portal for analyzing conformational changes in structures of Mycobacterium tuberculosis.
abstract: Initiation of the Tuberculosis Structural Consortium has resulted in the expansion of the Mycobacterium tuberculosis (MTB) protein structural database. Currently, 969 experimentally solved structures are available for 354 MTB proteins. This includes multiple crystal structures for a given protein under different functional conditions, such as the presence of different ligands or mutations. In depth analysis of the multiple structures reveal that subtle differences exist in conformations of a given protein under varied conditions. Therefore, it is immensely important to understand the conformational differences between the multiple structures of a given protein in order to select the most suitable structure for molecular docking and structure-based drug designing. Here, we introduce a web portal ( http://bmi.icmr.org.in/mtbsd/torsion.php ) that we developed to provide comparative data on the ensemble of available structures of MTB proteins, such as Cα root means square deviation (RMSD), sequence identity, presence of mutations and torsion angles. Additionally, torsion angles were used to perform principal component analysis (PCA) to identify the conformational differences between the structures. Additionally, we present a few case studies to demonstrate this database. Graphical Abstract Conformational changes seen in the structures of the enoyl-ACP reductase protein encoded by the Mycobacterial gene inhA.
authors.affiliation: Department of Biomedical Informatics, National Institute for Research in Tuberculosis, Chetpet, Chennai, 600 031, India.
authors.forename: Sameer
authors.initials: S
authors.lastname: Hassan
authors.affiliation: Department of Biomedical Informatics, National Institute for Research in Tuberculosis, Chetpet, Chennai, 600 031, India.
authors.forename: Manonanthini
authors.initials: M
authors.lastname: Thangam
authors.affiliation: Department of Biomedical Informatics, National Institute for Research in Tuberculosis, Chetpet, Chennai, 600 031, India.
authors.forename: Praveen
authors.initials: P
authors.lastname: Vasudevan
authors.affiliation: AU-KBC Research Centre, Madras Institute of Technology, Anna University, Chromepet, Chennai, India.
authors.forename: G Ramesh
authors.initials: GR
authors.lastname: Kumar
authors.affiliation: Department of Biomedical Informatics, National Institute for Research in Tuberculosis, Chetpet, Chennai, 600 031, India.
authors.forename: Rahul
authors.initials: R
authors.lastname: Unni
authors.affiliation: Department of Biomedical Informatics, National Institute for Research in Tuberculosis, Chetpet, Chennai, 600 031, India.
authors.forename: P K Gayathri
authors.initials: PK
authors.lastname: Devi
authors.affiliation: Department of Biomedical Informatics, National Institute for Research in Tuberculosis, Chetpet, Chennai, 600 031, India. hannatrc@yahoo.com.|Department of Clinical Research, National Institute for Research in Tuberculosis, Chetpet, Chennai, 600 031, India. hannatrc@yahoo.com.
authors.forename: Luke Elizabeth
authors.initials: LE
authors.lastname: Hanna
mesh_terms: D000995:Antitubercular Agents / Q000737:chemistry / Q000494:pharmacology; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry*; D020134:Catalytic Domain; D019295:Computational Biology / Q000379:methods; D030562:Databases, Protein; D055808:Drug Discovery; D008024:Ligands; D008958:Models, Molecular; D009169:Mycobacterium tuberculosis / Q000737:chemistry*; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D021281:Quantitative Structure-Activity Relationship; D064878:Web Browser
chemical_list: D000995:Antitubercular Agents; D001426:Bacterial Proteins; D008024:Ligands
keywords: Principal component analysis; Proteins; RMSD; Structures; Torsion angles