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| Feng Ding, University of North Carolina |
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| Dr. Feng Ding graduated in 1997 from Nanjing University, China and received his PhD in physics in 2004 from Boston University. Now he is a postdoctoral fellow in the department of Biochemistry and Biophysics of the University of North Carolina at Chapel Hill. His research mainly focuses on understanding protein folding, misfolding and aggregation. Currently, he is interested in multi-scale modeling of proteins by combining coarse-grained protein models with discrete molecular dynamic simulations and all-atom calculations using molecular mechanic simulations.
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Direct observation of protein folding, misfolding and prion-like conformational infectivity
Feng Ding, Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, 303 Mary Ellen Jones, CB#7260, Chapel Hill, NC 27599, USA
Protein conformational transition from alpha-helices to beta-sheets precedes aggregation of proteins implicated in many diseases, including Alzheimer's and prion diseases. Direct characterization of such transition is often hindered by the complicated nature of the interaction network among amino acids. A recently engineered small protein-like peptide with a simple amino acid composition features a temperature-driven alpha-helix to beta-sheets conformational change. Here, we study the conformational transition of this peptide by molecular dynamics simulations. We find a critical temperature, below which the peptide folds into an alpha-helical coiled-coil state, and above which the peptide misfolds into beta-rich structures with a high propensity to aggregate. The structures adopted by this peptide during low temperature simulations have a backbone root mean square deviation less than 2 Angstroms from the crystal structure. At high temperatures, this peptide adopts an amyloid-like structure, which is mainly comprised of coiled anti-parallel beta-sheets with the cross-beta signature of amyloid fibrils. Strikingly, we directly observe "infective" conformational conversions, where an alpha-helix is converted into a beta-strand by proximate stable beta-sheets with exposed hydrophobic surfaces and unsaturated hydrogen bonds. Our study suggests a possible molecular mechanism of the seeded aggregation process as proposed by Prusiner for the infectivity of prions.
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