Abstract

Proteins are amazing three-dimensional machines that carry out life’s essential processes. Modern methods in structural biology are enabling us to see these structures at work in ever-increasing molecular detail, and recent innovations in computational methods have revolutionised our ability to design new proteins at will. Yet the most fundamental process of all, how proteins fold and assemble into complex machines, remains mysterious. Errors of protein folding can give rise to devastating diseases, such as Alzheimer’s and Parkinson’s diseases and type II diabetes. Given the enormous burden of these, and other, disorders associated with protein misfolding, understanding how folding’s fold has never been more important.

In this lecture I will survey our current knowledge of protein folding; discuss how Alphafold and other computational methods are revolutionising our understanding of protein structure and behaviour; and share some of our newest discoveries in our quest to elucidate how proteins misfold and cause disease. Progress in this field is moving apace, yielding a plethora of new discoveries, enormous scientific excitement, and realistic hope that therapies to combat diseases of protein folding will soon be within our grasp.