Computer Simulations of Alzheimers Amyloid β-Protein Folding and Assembly

Pathological folding and aggregation of the amyloid  -protein (A ) are widely perceived as central to under- standing Alzheimer's disease (AD) at the molecular level. Experimental approaches to study A self-assembly are lim- ited, because most relevant aggregates are quasi-stable and inhomogeneous. In contrast, simulations can provide signifi- cant insights into the problem, including specific sites in the molecule that would be attractive for drug targeting and de- tails of the assembly pathways leading to the production of toxic assemblies. Here we review computer simulation ap- proaches to understanding the structural biology of A . We discuss the ways in which these simulations help guide ex- perimental work, and in turn, how experimental results guide the development of theoretical and simulation approaches that may be of general utility in understanding pathologic protein folding and assembly.