Professor John Straub
Department of Chemistry
Boston University
Boston, Massachusetts

Monday, January 28, 2002
3:00 pm (CT)
3269 Beckman Institute

Abstract

Recent work on the simulation and modeling of the structure, dynamics and activity of the Alzheimer's beta-amyloid peptide will be presented. A focus of our work will be on the validation of the computational model for the structure and dynamics of the Ab-peptide in aqueous solution. Direct comparison is made between the simulated structure and dynamics and observations from NMR and quasielastic light scattering experiments. Our simulation results on both wild type and mutant peptides allow for the identification of key intrapeptide interactions that stabilize the monomeric peptide structure and which are related to its aggregational propensity. The specific role of these interactions in defining the equilibrium fluctuations in the E22Q ``Dutch mutant'' peptide, which shows significantly enhanced propensity for aggregation relative to the wild type peptide, will be described. A detailed analysis of the equilibrium and dynamic aspects of the hydration of the Ab- peptide will be presented. The observations will be used to explain the relation of the peptide hydration and dehydration to its aggregational propensity and activity. Simulations using an explicit solvation model and an implicit Generalized Born solvation model will be compared and contrasted. I will conclude with a discussion of our efforts to derive coarse-grained ``minimal models'' suitable for the computational study of peptide and protein aggregation.

Tea and coffee will be served in R3151 Beckman Institute at 2:15pm.