G-protein coupled receptors (GPCRs) constitute one of the main targets for the pharmaceutical industry. For drug discovery programs, molecular dynamics (MD) techniques are increasingly gaining importance (Borhani & Shaw, 2012) as they provide a way to analyze the behavior of macromolecules such as GPCRs through time. For this reason, we are developing GPCRmd (www.gpcrmd.org): a database to store and display MD simulations of GPCRs from all over the world. This database will be linked to the highly renowned GPCRdb database (www.gpcrdb.org).
In particular, this project is centered on the creation of an online tool for the analysis of intra- and intermolecular interactions and their stability derived from GPCR dynamics. The analysis tool will be based on GetContacts (https://getcontacts.github.io/) scripts, which offers a way to precisely calculate different types of interactions (hydrogen bonds, water bridges, …) formed between the residues of a molecular system in a MD simulation. It will be designed as an easy, user-friendly web tool allowing researchers with different expertise (e.g. biologists, medicinal chemists, pharmacologists) to browse and exploit simulation data.
Once the tool is completed, we will study how inter- and intramolecular interaction networks are affected by (i) evolution and (ii) polymorphism across different GPCRs, which could be ultimately useful for drug design studies.
Borhani, D. W., & Shaw, D. E. (2012). The future of molecular dynamics simulations in drug discovery. Journal of Computer-Aided Molecular Design, 26(1), 15–26. https://doi.org/10.1007/s10822-011-9517-y
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Authors and affiliation:
David Aranda-Garcia, Mariona Torrens-Fontanals, Ismael Rodriguez-Espigares and Jana Selent
GPCR drug discovery group, Research Programme on Biomedical Informatics (GRIB), Universitat Pompeu Fabra (UPF) – Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain