- Research Grants
|Support type:||Scholarships in Brazil - Post-Doctorate|
|Effective date (Start):||April 01, 2007|
|Effective date (End):||June 30, 2010|
|Field of knowledge:||Physical Sciences and Mathematics - Chemistry|
|Principal Investigator:||Munir Salomao Skaf|
|Home Institution:||Instituto de Química (IQ). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil|
Nuclear hormone receptors form an important family of trascription factors. They are DNA-binding proteins, and are regulated by the binding of hormones (Estrogen, Thyroid Hormone, Retinoic Acid, among others). The specific binding to DNA and regulated hormone binding determine whether a gene will be transcripted or repressed. Since 1995 several three-dimensional structures of the LBD of nuclear receptors were obtained, allowing for important advances in the comprehension of the molecular biology of hormone recognition. However, in spite of the fact that new structures were obtained for different receptors, the role of the dynamics of the receptors remained fundamentally unknown. As a graduate student, I studied everal aspects of the dynamics of nuclear hormone receptors and their role in the biological function of these proteins. We obtained results that associate the dynamics of the receptors to their function in various different areas, such as hormone binding and dissociation, ligand selectivity and denaturation mechanisms, for example. The use of new techniques for expanding these results may complement our studies in a important way, leading to one of the most comprehensive set of data on the dynamics of nuclear hormone receptors. Three main new areas of research are proposed in this project:1. The study of ligand entry into the receptors. 2. The identification of transition states of protein denaturation. 3. To obtain optimal dissociation paths.