Lattice Moels of Protein Folding North Carolina State University北卡罗来纳州立大学的格子模型的蛋白质折叠.pptVIP

Thermodynamic and Kinetic Origins of Alzheimers and Related Diseases: a Chemical Engineers Perspective  Carol K. Hall Department of Chemical Biomolecular Engineering North Carolina State University Protein Folding: The ABCs A. A protein is a chain of amino acid residues arranged in a unique sequence. B. There are 20 possible sidechains. C. Physiological proteins exist in the folded or “native” state, the state with the lowest free energy. D. Proteins unfold into a “random coil” if temperature raised or denaturant (urea, GuHCl) added. E. Of all the forces thought to govern protein folding, hydrophobicity and hydrogen bonding are considered most important. Amyloidoses: Diseases characterized by the abnormal aggregation of proteins into ordered structures, called “fibrils” or “amyloid.” Alzheimer’s Disease 100 years ago --Dr. Alois Alzheimer described abnormal clumps in brain of deceased dementia patient, Auguste D. Clinical symptoms: severe dementia, loss of memory motor skills---- death Late onset disease : 5-10% of 65-74 year olds, 50% of 85+ year olds 4.5 million Americans Costs $100 billion/year US Research Budget $650 million/year. Structure of Amyloid Fibrils Fibrils are ordered aggregates of peptides characterized by cross-beta structure Issues in Amyloid Disease Research Identity of toxic species--- early oligomers or fibrils? Kinetics of fibril nucleation and growth Structure of fibrils Interactions with inhibitors Objective To develop a computational tool that : allows investigation (particularly visualization) of spontaneous fibril formation. reveals the basic physical principles underlying fibril formation . Polyalanine– A Model System for Studying Protein Fibrillization Speculation - fibril formation is natural consequence of peptide geometry, hydrogen-bonding capability and hydrophobic interactions under slightly-denatured, concentrated conditions. Polyalanine peptides form fi