title: Simulations as analytical tools to understand protein aggregation and predict amyloid conformation.
abstract: Computational tools are increasingly being applied to solve the protein aggregation problem, providing insight into amyloid structures and aggregation mechanisms. The paradigm of Abeta amyloid structure elucidation provides an example of an innovative experimental design and endeavor, echoing the computational testing of possible molecular associations, all reflected in the current Ma-Nussinov-Tycko model of the Abeta amyloid. Simulations have shown that dimer formation can lock some misfolded conformations, and catalyze the shift of the equilibrium away from the native state. In most cases, a stable amyloid seed requires at least two-layered beta-sheets with properly registered side-chains. Under kinetic control, the final protein aggregations are the outcome of maximizing the van der Waals interactions between side chains and backbone hydrogen bonds.
authors.affiliation: Basic Research Program, SAIC-Frederick Inc, Center for Cancer Research, Nanobiology Program, NCI-Frederick, Frederick MD 21702, USA.
authors.forename: Buyong
authors.initials: B
authors.lastname: Ma
authors.forename: Ruth
authors.initials: R
authors.lastname: Nussinov
mesh_terms: D000682:Amyloid / Q000737:chemistry*; D003198:Computer Simulation; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D011237:Predictive Value of Tests; D011487:Protein Conformation
chemical_list: D000682:Amyloid