G protein–coupled receptors (GPCRs) are major targets for the pharmaceutical industry, being involved in a large number of physiological processes and pathologies, including neurodegenerative and psychotic disorders (1). Although GPCRs have been extensively studied over the past decades, the molecular details of underlying mechanisms responsible for many critical regulatory processes of this protein superfamily remain elusive (2).
An attractive approach to elucidate these mechanisms are molecular dynamics (MD) simulations, a potent computational technique capable of generating simulations of the evolution of molecular processes throughout time (3). Yet, molecular dynamics present one drawback: obtaining sufficient simulation data to achieve a robust sampling of structural conformations related to GPCR signaling is, computationally, highly expensive. In this project, we aim to overcome this drawback by using a technique known as volunteer distributed computing. It consists in using idle resources of personal computers owned by volunteers from all over the world to solve large computational problems such as the generation of extensive molecular simulations data (4).
In this respect, this project aims to create Brainstorm@home, a volunteer distributed computing platform focused on the study of the role of GPCRs in brain-related diseases and disorders. Combining the high-resolution structural information of MD simulations and the computational resources of volunteer distributed computing, we will be able to understand relevant molecular processes in GPCR signaling, bridging the gap towards new pharmacological treatments targeting GPCRs.
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- Latorraca, N. R., Venkatakrishnan, A. J. & Dror, R. O. GPCR Dynamics: Structures in Motion. Chem. Rev. 117, 139–155 (2017).
- Rosenbaum, D. M., Rasmussen, S. G. F. & Kobilka, B. K. The structure and function of G-protein-coupled receptors. Nature 459, 356–63 (2009).
- Hadley, C. Biologists think bigger. EMBO Rep. 5, 236–238 (2004).
Authors and affiliation:
Mariona Torrens-Fontanals 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
M.T.-F. acknowledges financial support from the Spanish Ministry of Education, Culture and Sport (FPU16/01209), J.S. acknowledges financial support from Instituto de Salud Carlos III FEDER (PI15/00460 and PI18/00094).