CHOPIN: a web resource for the structural and functional proteome of Mycobacterium tuberculosis

Abstract

Tuberculosis kills more than a million people annually and presents increasingly high levels of resistance against current first line drugs. Structural information about Mycobacterium tuberculosis (Mtb) proteins is a valuable asset for the development of novel drugs and for understanding the biology of the bacterium; however, only about 10% of the ∼4000 proteins have had their structures determined experimentally. The CHOPIN database assigns structural domains and generates homology models for 2911 sequences, corresponding to ∼73% of the proteome. A sophisticated pipeline allows multiple models to be created using conformational states characteristic of different oligomeric states and ligand binding, such that the models reflect various functional states of the proteins. Additionally, CHOPIN includes structural analyses of mutations potentially associated with drug resistance. Results are made available at the web interface, which also serves as an automatically updated repository of all published Mtb experimental structures. Its RESTful interface allows direct and flexible access to structures and metadata via intuitive URLs, enabling easy programmatic use of the models.Database URL: http://structure.bioc.cam.ac.uk/chopin

Decoding the similarities and differences among mycobacterial species

“…We inspected ML2177c for its druggability by predicting the hotspots in the protein structure model. We first modeled the protein structures using our in-house automated modeling pipeline ( Vivace ) [ 18 ], followed by prediction of the druggable sites using our software for fragment hotspot mapping ( Fig 6A ) [ 60 ], which provides insights into the ligand binding site for the target. Using the known oligomeric structure for uridine phosphorylase for Shewanella oneidensis (PDB ID: 4R2X, 30% identity with ML2177c) as a template, we modeled the hexameric complex for ML2177c.…”

“…Since the determination of the complete genome sequence of M . tuberculosis , there have been efforts to develop inventories that record information on open reading frames (ORFs) annotations and gene expression [ 8 – 11 ], drug resistance mutations and drug targets [ 12 – 15 ], phylogenetic relationships [ 16 , 17 ], pathogenomics, and structure and function annotation of the mycobacterial genome [ 18 , 19 ].…”

Early diagnosis and effective treatment regimens are the keys to tackle antimicrobial resistance in tuberculosis (TB): A report from Euroscicon's international TB Summit 2016

“…To this end Prof Blundell's group has been working on Chopin, which inherits the information of the known structures for around 400 proteins and uses it to predict models for the remaining 3,500 protein structures. 114 Based on the information in publicly available databases; interactions, ligands and the oligomeric states of many of the proteins can be deciphered. This information can then be fed into structure-guided, fragmentbased approaches in drug discovery.…”

SInCRe—structural interactome computational resource forMycobacterium tuberculosis

“…The CHOPIN ( 11 ) database ( http://structure.bioc.cam.ac.uk/chopin ) assigns structural domains and generates homology models for 2911 sequences, corresponding to ∼73% of the proteome. Conformational states, characteristic of different oligomeric states and ligand binding, reflect various functional states of the proteins.…”

“…Structural annotation of M . tuberculosis proteome ( 10 ) and CHOPIN ( 11 ) database provided structural data for many proteins. PocketDepth ( 12 ), PocketMatch ( 13 ) and PocketAlign ( 14 ) algorithms are used for binding site prediction and comparison.…”