Study of the molecular interactions involved in the aggregate formation of Superoxide Dismutase 1 (SOD1) and your Thermodynamics aspects using Molecular Dynamics with excited Normal Modes and data mining techniques.
The human enzyme Cu, Zn-SOD is a homodimer of 35-kDa (Rumfeldt, 2009) in which each monomer binds to a zinc atom and a copper atom. The copper is directly involved in catalysis reactions while zinc has structural function in the active site region. This enzyme converts superoxide anion into hydrogen peroxide and molecular oxygen. This research project has as main objectives: i) understand the molecular interactions involved in the formation of the SOD1 aggregates; ii) identify patterns (flexible and solvent accessible area and others) in the SOD1 mutants that are correlated with aggregate formation and with different diseases, iii) study and understand the role of copper (Cu) and zinc (Zn) to stability of the SOD1 structure and propensity to aggregate formation, iv) contribute to understanding, more generally, the protein aggregation mechanism. The research project will be developed in Computational Biology and Bioinformatics Laboratory of UFABC in collaboration with Dr. David Perahia who specializes in Normal and Dynamic modes Molecular analysis techniques. Studies on the mechanisms and aggregates involved with diseases can help in the understanding of them and the development of new drugs. More specifically, the understanding of the molecular interactions involved in the formation of the SOD1 aggregates and their mutants are important and contribute to the understanding of the molecular mechanisms involved in neurodegenerative diseases such as Amyotrophic Lateral Sclerosis. (AU)
Articles published in Agência FAPESP Newsletter about the research grant: