I³MS - Rossetti Seminar
Dr. Giulia Rossetti - Computational Approaches to Molecular Disease Mechanisms
Computational Biophysics, German Research School for Simulation Science, Jülich
The use of molecular simulation and structural bioinformatics to predict the structure, dynamics, and energetics of biological systems is a key approach to molecular medicine. Diseases including neurodegeneration, HIV and cancer are indeed related to specific molecular events in the cell, the understanding of which is a crucial step for drug-design approaches. We combine different computational methods in a powerful strategy aimed at dissecting structural and energetic facets of molecular events related to human diseases. Among these, neurodegenerative diseases (NDs) represent an interesting example. The common trait of NDs is the change in the shape of a key protein (“misfolding”), which brings cellular dysfunctions and aggregation and the presence of amyloid plaques in the brain. Unraveling the key factors that stabilize the native structure (or the three-dimensional shape) of proteins subjected to misfolding in neurodegeneration is highly challenging, as several of these proteins are (partially or totally) naturally unfolded, existing as dynamic ensembles of interconverting structures. By using multi-scale modeling, from classical to ab initio MD, from bioinformatics to advanced free energy calculations we can clarify crucial aspect of ND for future drug-design approaches.