Computational structural analysis of proteins of Mycobacterium tuberculosis and a resource for identifying off-targets

• Published in: Journal of molecular modeling Vol. 18; no. 8; pp. 3993 - 4004
• Main Authors: Hassan, Sameer, Debnath, Abhimita, Mahalingam, Vasantha, Hanna, Luke Elizabeth
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.08.2012
• Subjects: Amino Acid Motifs; Amino Acid Sequence; Bacterial Proteins - chemistry; Characterization and Evaluation of Materials; Chemistry; Chemistry and Materials Science; Computer Appl. in Life Sciences; Computer Applications in Chemistry; Computer Simulation; Conserved Sequence; Databases, Protein; Models, Molecular; Molecular Medicine; Molecular Sequence Data; Mycobacterium tuberculosis; Original Paper; Protein Structure, Tertiary; Proteome - chemistry; Structural Homology, Protein; Theoretical and Computational Chemistry; Proteins; Structures; Structural homologues; Off-targets
• ISSN: 1610-2940; 0948-5023
• DOI: 10.1007/s00894-012-1412-5

Advancement in technology has helped to solve structures of several proteins including M. tuberculosis (MTB) proteins. Identifying similarity between protein structures could not only yield valuable clues to their function, but can also be employed for motif finding, protein docking and off-target identification. The current study has undertaken analysis of structures of all MTB gene products with available structures was analyzed. Majority of the MTB proteins belonged to the α/β class. 23 different protein folds are used in the MTB protein structures. Of these, the TIM barrel fold was found to be highly conserved even at very low sequence identity. We identified 21 paralogs and 27 analogs of MTB based on domains and EC classification. Our analysis revealed that many of the current drug targets share structural similarity with other proteins within the MTB genome, which could probably be off-targets. Results of this analysis have been made available in the Mycobacterium tuberculosis Structural Database ( http://bmi.icmr.org.in/mtbsd/MtbSD.php/search.php ) which is a useful resource for current and novel drug targets of MTB.