Isaac Amela Abellan Laboratory of Bioinformatics

1. Isaac Amela Abellan Laboratory of Bioinformatics Institute of Biotechnology and Biomedicine (IBB) Autonomous University of Barcelona (UAB) CASE OF STUDY 2: COMMONALTIES OF, AND DIFFERENCES BETWEEN HORMONAL PATHWAYS IN BREAST, ENDOMETRIUM, AND PROSTATE CANCER In my point of view, and considering the tools I use in our laboratory, I think that I can contribute to the presented case of study through this approaches: • Sequence, structure and functional study of the different nuclear homone receptors, steroid hormones and chemical drug molecules involved. • Theorical molecular modelling of the interaction mechanisms between the molecules described above. • DNA microarray analysis of relevant data available about this item.

2. Isaac Amela Abellan Laboratory of Bioinformatics Institute of Biotechnology and Biomedicine (IBB) Autonomous University of Barcelona (UAB) • SEQUENCE, STRUCTURE AND FUNCTIONAL STUDY: • All the molecules that take part in the case of study could be analysed using several on line bioinformatics tools. • Moreover, all these data will be compared and complemented with bibliography to understand and to confirm our preliminary hypothesis (NCBI, http://www.ncbi.nlm.nih.gov/ ). • Molecular visualization will be done using for example: • UCSF Chimera an Extensible Molecular Modeling System. • Pettersen, E.F., Goddard, T.D., Huang, C.C., Couch, G.S., Greenblatt, D.M., Meng, E.C., and Ferrin, T.E. "UCSF Chimera - A Visualization System for Exploratory Research and Analysis." • J. Comput. Chem.25(13):1605-1612 (2004). • RasWin Molecular Graphics 2.7.2.1.1 • Sayle RA, Milner-White EJ. • RASMOL: biomolecular graphics for all. • Trends Biochem Sci. 1995 Sep;20(9):374. • Glaxo Wellcome Medicines Research Centre, Stevenage, Herts, UK.

3. Isaac Amela Abellan Laboratory of Bioinformatics Institute of Biotechnology and Biomedicine (IBB) Autonomous University of Barcelona (UAB) 2. MODEL THE MOLECULAR INTERACTION MECHANISM: • We will be able to either explore the possibility to perform a de novo model or to compare it with an already known interaction mechanisms of the different nuclear hormone receptors, steroid hormones and chemical drug molecules. This will be done using Docking Web Servers like ClusPro or Docking Local Programs like: • BiGGER (Biomolecular complex Generation with Global Evaluation and Ranking), an automated protein-protein docking algorithm integrated in the Chemera 3.0 software package. • Palma, P.N., Krippahl, L., Wampler, J.E. and Moura, J.J.G. 2000. • "BiGGER: A new (soft) docking algorithm for predicting protein interactions." Proteins: Structure, Function, and Genetics 39:372-384. • Escher NG of the VEGA ZZ 2.0.6 program under the VEGA project. • A. Pedretti, L. Villa, G. Vistoli."VEGA - AN OPEN PLATFORM TO DEVELOP CHEMO-BIO-INFORMATICS APPLICATIONS, USING PLUG-IN ARCHITECTURE AND SCRIPT" PROGRAMMING“.J.C.A.M.D., Vol. 18, 167-173 (2004).

4. Isaac Amela Abellan Laboratory of Bioinformatics Institute of Biotechnology and Biomedicine (IBB) Autonomous University of Barcelona (UAB) 3. DNA MICROARRAY ANALYSIS: • The data of several DNA microarray experiments are reported and will be analysed. We will be able to study for example the GEO Profiles or GEO Datasets under the NCBI HomePage (http://www.ncbi.nih.gov/). • The DNA array data for a relevant experiment is available at: http://discover.nci.nih.gov/nature2000/natureintromain.jsp “A Gene Expression Database for the Molecular Pharmacology of Cancer”. Nature Genetics, volume 24, no 3 March 1st, 2000 pp:236-244. • The data above described is used as a framewok for the study of gene expression networks in a Web Tool developed by my research group colleagues and this will be applied to gain insight into the hormonal pathways of the three different cancers. http://revolutionresearch.org