Amino Acid and Peptide Asssembly: Mechanisms and Structures

University Of California-Santa Barbara, Santa Barbara CA

Investigators

Abstract

In this project funded by the Chemical Structure, Dynamic & Mechanism B Program of the Chemistry Division, Professor Michael T. Bowers at the University of California at Santa Barbara are investigating the mechanism of peptide assembly. Peptide and protein assemblies can contribute to many devastating diseases such as Alzheimer's disease because of amyloid formation. This is an active area of research both for its fundamental importance and its potential impacts on health. Through the studies on model amino acids and peptides, factors that control larger peptide and protein assembly can be learned, which can help the development of new therapeutic agents. The project is well suited for the education of scientists at all levels, including those underrepresented in science. Outreach activities to high school students in the Ventura and Santa Barbara areas are also part of the funded project. A free website that allows the accurate and rapid calculation of cross sections of model structures is also supported by this grant. Specifically, this grant is focused on the assembly of amino acids and small peptides. In these studies, Ion Mobility based Mass Spectrometry (IMS-MS) is used as the main tool. In collaboration with the group of Gert von Helden at the Fritz Haber Institute in Berlin, IMS-MS is coupled with the Fritz Haber free electron laser to do spectroscopy on size and shape selected oligomers of both amino acids and small peptides. The overarching goal is to understand the molecular mechanism of the amyloid cascade that is often observed for peptides and proteins in systems related to many devastating diseases. The amyloid hypothesis states that peptides natively fold and isotropically assemble until at a system dependent size they rearrange to beta sheet and rapidly add monomers to form fibrils. The group, in past NSF support periods, observed this process for specific peptide systems. The current project seeks to understand these observations and to develop an algorithm that can accurately predict the predilection of a peptide or protein to form amyloid knowing only the primary structure.