Xavier Barril

Universitat de Barcelona

Experimental Sciences & Mathematics

Xavier Barril's research focuses on the discovery of bioactive molecules exploiting unusual mechanisms of action through a combined use of computational and experimental techniques. His group also develops new computational tools (druggability predictions, docking, dynamic undocking) and strives to improve the molecular understanding of pharmacologically important biological events (e.g. binding kinetics, allosterism). Prof. Barril received his Ph.D. from the Barcelona University (UB) in 2001 for theoretical studies on the molecular recognition processes. He then joined Vernalis (Cambridge, UK), where he was involved in a range of drug discovery projects. In 2005 he was appointed ICREA Research Professor and went back to the UB. Prof. Barril has co-authored more than 70 scientific publications as well as 8 patents. He is also co-founder of Minoryx Therapeutics, a company focusing in the development of new treatments for rare diseases.

Research interests

We are interested in discovering bioactive molecules (chemical probes) as a means to validate new points of pharmacological intervention. We aim to expand the so-called druggable genome by targeting so-far unexploited sites that elicit a biological response through non-standard mechanisms of action, such as conformational trapping, stabilisation of protein-protein complexes or allosterism. To achieve this objective we employ a multi-disciplinary and question-driven approach that combines computational, biophysical and biological techniques. We are particularly strong in computer-aided drug design and we develop new computational approaches that enable us to tackle such novel and difficult targets with confidence.

Selected publications

- Ruiz-Carmona S, Schmidtke P, Luque FJ, Baker L, Matassova N, Davis B, Roughley S, Murray J, Hubbard R & Barril X 2017, 'Dynamic undocking and the quasi-bound state as tools for drug discovery', Nature Chemistry, 9, 201–206.    

- Arcon JP, Defelipe LA, Modenutti CP, Lopez ED, Alvarez-Garcia D, Barril X, Turjanski AG & Marti MA 2017, 'Molecular Dynamics in Mixed Solvents Reveals Protein-Ligand Interactions, Improves Docking, and Allows Accurate Binding Free Energy Predictions', Journal of Chemical Information and Modeling, 57, 4, 846-863.

- Duran-Frigola M, Siragusa L, Ruppin E, Barril X, Cruciani G & Aloy P 2017, 'Detecting similar binding pockets to enable systems polypharmacology', Plos Computational Biology, 13, 6, e1005522.

- Arimany-Nardi C, Claudio-Montero A, Viel-Oliva A, Schmidtke P, Estarellas C, Barril X, Bidon-Chanal A & Pastor-Anglada M 2017, 'Identification and Characterization of a Secondary Sodium-Binding Site and the Main Selectivity Determinants in the Human Concentrative Nucleoside Transporter 3', Molecular Pharmaceutics, 14, 6, 1980-1987.

- Westermaier Y, Ruiz-Carmona S, Theret I, Perron-Sierra F, Poissonnet G, Dacquet C, Boutin JA, Ducrot P & Barril X 2017, 'Binding mode prediction and MD/MMPBSA-based free energy ranking for agonists of REV-ERB alpha/NCoR', Journal Of Computer-aided Molecular Design, 31, 8, 755-775.

- Radusky LG, Ruiz-Carmona S, Modenutti C, Barril X, Turjanski AG & Martí MA 2017 'LigQ: a WebServer to select and prepare ligands for virtual screening', Journal of Chemical Information and Modelling, 57, 8,1741−1746 

- Barril X 2017, 'Computer-aided drug design: time to play with novel chemical matter', Expert Opinion On Drug Discovery, 12, 10, 977-980.

Selected research activities

Research stay: Five months stay in the group of Prof. Kodadek at the Scripps Research Institute (Jupiter, FL) - Fulbright program.

PhD thesis supervisor of S. Ruiz Carmona, "VS for novel mechanisms of action: applications and methodological developments" (UB). 20 Jan 2017