Abstract

Non-covalent interactions precede almost all important biological functions. This is particularly so for peptides and proteins where they often assemble into myriad structures before they reach their active state. There is also a down side to such assembly as exemplified by the many amyloid systems that occur and provide the basis for many devastating diseases such as Alzheimer’s Disease, Parkinson’s Disease, Type 2 Diabetes and many more. These can occur for systems as small as amino acids (phenylketonuria) or proteins of many hundreds of amino acids (taupathies). As a consequence it is of prime importance to understand the factors that drive these systems to self assemble so that effective therapeutic strategies and agents can be designed and tested. Here we will introduce the problem, why it is so hard to study, briefly describe the methods we use to attack it and give our latest results. We will demonstrate that ultra soft ion mobility methods, especially when coupled to mass spectrometry, high level modeling and most recently to spectroscopy offer hope in understanding the size and conformation specific growth of amyloid systems, while other spectroscopies are ineffective. We will focus in this talk on the basic peptide assembly mechanism rather than directly on disease, although that will also play a part.