Cystic fibrosis (CF) is a genetic disease, caused by CFTR which encodes a chloride and bicarbonate transporter expressed in exocrine epithelia throughout the body.
CandActCFTR is a curated compound database which annotates the chemical structure library with information on where and how in the protein life cycle a compound likely interacts, thus comprising a good starting point for modelling the disease and enhancing ligand based approaches (e.g. via eu-openscreen).
Our application CandActBase, adaptable also to other use cases than CFTR compound analysis, and the CandActCFTR data content is provided at https://gitlab.gwdg.de/mnieter1/CandActBase.
In the current extension of CandActCFTR, this ligand-based approach will be complemented by structure-based annotations, including the means to predict the interactions between CandActCFTR substances and CFTR by using existing molecular dynamics trajectories, and by adding more organisation and annotation modules. This approach will help in ranking putative therapeutic substances according to their potential to bind CFTR. Moreover, it will be further extended by integrating results from high-throughput screens from collaborators, helping to rank putative therapeutic substances.
Furthermore CandActCFTR will use public gene expression data to assess transcriptome profiles of CandActCFTR substances and compare differentially expressed genes to gene sets with known relevance for CFTR function, helping to rank putative therapeutic substances according to their potential to modify the cellular transcriptome in favor of CFTR function via Göttingen institutes curated TRANScription FACtor database - TRANSFAC.