On a molecular level, the onset of Alzheimer, Parkinson, and other neurodegenerative diseases is related to aberrant protein aggregation and amyloid fibril assembly. To devise therapeutic approaches that block or slow down these processes, a detailed biophysical understanding of molecular interactions and structural transitions is required. It is now known that the assembly of pathological amyloid structures involves at least two key events - (1) an initial formation of large, loosely organized multiprotein aggregates and (2) growth of existing amyloid fibrils by addition of individual protein molecules. Both processes play a central role in amyloid-related diseases, but remain poorly understood. Computational modeling and simulations are expected to play an important role in the studies of amyloid assembly.

Assistant professor Dmitri Klimov of the Department of Bioinformatics and Computational Biology is studying the process of assembly of Alzheimers Abeta peptides into amyloid fibrils using molecular dynamics simulations and all-atom modeling. The goal of his research is (i) to probe the formation of Abeta oligomers, (ii) to simulate deposition of Abeta peptides on pre-existing Alzheimers fibrils, (iii) and to investigate the function of molecular inhibitors to fibril growth.

Molecular dynamics simulations of amyloid assembly are computational intensive and at a minimum must span nano- to microsecond timescales. As a result they critically depend on advanced sampling algorithms and powerful parallel computing resources. The SGI supercomputer installed at George Mason University provides a unique opportunity to extend simulations of Abeta amyloid formation to new, previously inaccessible timescales. Ultimately, simulations of amyloid assembly and growth are expected to assist in development of new therapeutic strategies against Alzheimers disease.