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Seminars, events & talks

Monday, 25th March, 2013

Computational Biophysics

Biomolecular Simulation 2013

25-27 March 2013, Nottingham, UK.

Speaker: Gianni de Fabritiis

Thursday, 21th March, 2013, 11:00-12:00

GPCR drug discovery

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

Speaker: Inma Tur

Room Room Aula (473.10 - 4th floor)

Friday, 15th March, 2013, 12.00-13.00

Computational Biophysics

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

Thursday, 7th March, 2013, 11:00

GPCR drug discovery

Unraveling the mechanisms of tumorigenesis

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

Room Aula (473.10)

Thursday, 28th February, 2013, 11.00-12.00

Evolutionary Genomics

How orphan genes, novel domains and protein modularity help set the stage for genomic novelties and developmental shifts

Over the past years it became clear that many "novel" genes are indeed truly novel since they have not arisen in the wake of gene or whole genome duplications.

I will discuss the mechanisms of novel gene emergence across different taxa. I will also concentrate on the role which gene rearrangements play for the emergence of novel proteins with altered functions that may cause functional shifts and trigger developmental innovations.

Most shockingly, thousands of domain are completely lost along every lineage over several millions of years but only some tens of domains are newly formed. However, these novel domains seem to have a high adaptive value as they rapidly multiply in genomes and seem to confer a high fitness gains since they are mostly related to biotic and abiotic stress responses.

Speaker: Erich Bornberg-Bauer, Molecular Evolution and Bioinformatics Inst., University Muenster, Germany

Room Aula Room CRG (473.10)

Monday, 4th February, 2013

Computational Biophysics

Fragment based drug discovery by simulation

CDDD - Computationally Driven Drug Discovery, Istituto Italiano di Tecnologia (IIT), Geneve (Italy) 4-6 February 2013

Speaker: Gianni de Fabritiis

Friday, 25th January, 2013, 12.00

Computational Biophysics

Structural Bioinformatics applied to Bio-Nanotechnology

Speaker: Fernando Danilo González Nilo, Center for Bioinformatics and Integrative Biology (CBIB), Santiago de Chile, Chile.

Room Marie Curie

Friday, 7th December, 2012, 12:00 - 13:00

GPCR drug discovery

Pathway driven prediction of mutation impact in cancer

Josh Stuart, from the Systems Biology Group of the University of California, Santa Cruz, USA, uses data-driven approaches to identify and characterize genetic networks, investigates how they've evolved, and then uses them to 
simulate and predict cellular behavior. His approach is to design computational models and algorithms that integrate highthroughput molecular biology datasets to predict cellular- and organism-level phenotypes. He particularly focuses on elucidating altered signalling pathways in cancer cells that initiate and drive tumorgenesis and is developing models to predict the impact of mutations in human tissue and a patient's response 
to treatment. 

Speaker: Josh Stuart, Systems Biology Group-University of California, Santa Cruz, USA

Room Marie Curie Room

Thursday, 29th November, 2012, 11:00

Evolutionary Genomics

"Unequal evolution after gene duplication is mediated by positive selection"

Gene duplication plays a major role in genome evolution and is widely accepted to be an important source of new gene functions. Different scenarios have been proposed to explain the retention of the two copies: gain of an advantageous function by one of the copies (neofunctionalization), split of the ancestral function between the two copies (subfunctionalization) and, increased gene dosage advantage.
The analyses published so far have not conclusively identified any of these models as the dominating one. Taking advantage of the reasonable highquality mouse and rat genomes, we have obtained an exhaustive set of duplicated genes that were originated at different times during rodent evolution and measured the strength of purifying selection and of positive selection at different time periods. Our findings indicate that after gene duplication, the daughter copy typically evolves 3 to 5 times faster than the parental copy, and the impact of positive selection increases about 3.5 fold with respect to the ancestral gene. After the initial acceleration the rate gradually decreases until it reaches the levels observed before the duplication. In addition, only the faster evolving copy displays significant differences in tissueexpression patterns compared to the singlecopy ortholog. Our results provide strong evidence that neofunctionalization is the most common scenario driving the fate of recently duplicated rodent genes.

Speaker: Cinta Pegueroles - Biomedical Informatics - GRIB (IMIM/ UPF)

Room Aula (473.10)

Wednesday, 26th September, 2012

Computational Biophysics

Fragment based drug discovery by simulation

Drug Design 2012, Oxford, UK,  26-28 September, 2012

Speaker: Gianni de Fabritiis

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