Seminars, events & talks

Thursday, 27th June, 2013, 11:00-12:00

Visual phototransduction: from rhodopsin mutations to retinal disease

Rhodopsin is the visual pigment of the vertebrate retina responsible for light capture in the first molecular events of the complex process of vision. This photoreceptor protein has served as a prototypical model for G-protein coupled receptors (GPCRs) superfamily. Upon photoactivation, rhodopsin binds and activates the specific G- protein transducin. The details of this light-dependent activation, including the molecular interaction with transducin, have not been fully elucidated. Mutations in rhodopsin have been associated with the retinal degenerative disease retinitis pigmentosa (RP). The folding, degradation and aggregation of some of these mutant rhodopsins can be manipulated by drugs or molecular chaperones. Our goal is to deepen our knowledge of the molecular consequences of such mutations while gaining, at the same time, new insights into the structural requirements of the photoactivation process. We are also interested in the effect of lipids and metal ions on the structure, stability and function of rhodopsin, and the ligand protein interactions comparison between rhodopsin and cone opsin pigments. We will describe recent results on rhodopsin mutations associated to RP or potentially relevant for visual pigment evolution, the effect of docosohexaenoic acid lipid on the stability of purified rhodopsin and the kinetic differences between rhodopsin and red cone opsin ligand binding after photoactivation. Overall, our studies may enhance our understanding of the molecular mechanisms of phototransduction, the biology of GPCRs in general, and importantly, they may help develop potential approaches to treat RP caused by rhodopsin mutations.

(Supported by grants SAF2011-30216-C02-01 from MICINN, CIVP16A1861 from Fundación Ramón Areces, and Grups de Recerca Consolidats de la Generalitat de Catalunya (2009 SGR 1402).

Speaker: Pere Garriga, Department of Chemical Engineering, Universitat Politècnica de Catalunya (UPC)

Room Xipre (seminar 173.06-183.01), PRBB.

Tuesday, 18th June, 2013

Structure-Based Drug Design conference

BIO-IT, 19-21 June 2013, Cambridge, Massachusetts, USA.

Speaker: Gianni de Fabritiis

Sunday, 2nd June, 2013

Conference of the Russian Biophysical society

3-7 June 2013, Moscow, Russia.

Speaker: Gianni de Fabritiis

Wednesday, 29th May, 2013, 11:00

The isoform selection problem in genome-wide studies and its impact in alignment quality and positive selection

Speaker: Jose Luis Villanueva - Evolutionary Genomics (GRIB)

Room Aula (473.10)

Wednesday, 15th May, 2013, 11:00

Active intragenic enhancers and their effect in alternative transcription initiation

Speaker: Juan González-Vallinas, Evolutionary Genomics group, GRIB (IMIM-UPF)

Room Aula (473.10)

Sunday, 7th April, 2013

Conference of the american chemical society

8-11 April 2013 New Orleans,USA.

Speaker: Gianni de Fabritiis

Sunday, 24th March, 2013

Biomolecular Simulation 2013

25-27 March 2013, Nottingham, UK.

Speaker: Gianni de Fabritiis

Wednesday, 20th March, 2013, 11:00-12:00

High-resolution mapping of trans-acting associations in eQTL networks

Speaker: Inma Tur

Room Room Aula (473.10 - 4th floor)

Thursday, 14th March, 2013, 12.00-13.00

Using docking and molecular dynamics to design drugs

We have discovered by high-throughput fragment-based docking several novel chemotypes of potent (single-digit nanomolar) and selective tyrosine kinase inhibitors [1-4].  Explicit solvent molecular dynamics has played an important role for the in silico validation of binding modes and  the selection of compounds for testing in vitro.  Definitive validation of the binding mode has been obtained by X-ray crystallography in our group [1,2].  The most advanced of our tyrosine kinase inhibitors are active on a subset of the NCI 60 cancer cell lines.  Furthermore, some of our  inhibitors have shown good pharmacokinetic properties in mice (including oral bioavailability) and are being currently selected for testing in tumor xenograft models.

[1] K. Lafleur et al. Structure-based Optimization of Inhibitors of the Tyrosine Kinase EphB4. Part 2: Cellular Potency Improvement and Binding Mode Validation by X-ray Crystallography. J. Med. Chem. 56, 84, 2013.

[2] H. Zhao, J. Dong, K. Lafleur, C. Nevado, and A. Caflisch.
Discovery of a novel chemotype of tyrosine kinase inhibitors by fragment-based docking and molecular dynamics. ACS Med. Chem. Lett. 3, 834, 2012.

[3] H. Zhao, D. Huang, and A. Caflisch. Discovery of tyrosine kinase inhibitors by docking into an inactive kinase conformation generated by molecular dynamics. ChemMedChem 7, 1983, 2012.

[4] K. Lafleur et al. Structure-based optimization of potent and selective inhibitors of the tyrosine kinase erythropoietin producing human hepatocellular carcinoma receptor B4 (EphB4).
J. Med. Chem. 52, 6433, 2009.

Speaker: Amedeo Caflisch, Computational Structural Biology, University of Zurich, Switzerland.

Room Seminar room 473.10

Wednesday, 6th March, 2013, 11:00

Unraveling the mechanisms of tumorigenesis

Speaker: Abel Gonzalez-Perez & David Tamborero - Biomedical Genomics, GRIB-UPF

Room Aula (473.10)

Site Information