Abstract:

Local interactions within and between proteins (or interacting objects in general) inherently determine the resulting global structure, whether that be a monomeric protein structure, a dimer or multimer, or a larger aggregate consisting of tens to thousands of proteins. In this presentation, I begin by delving into the range of emergent multi-body structures that can arise from slight changes in environmental or structural parameters that ultimately affect the local interaction patterns between monomers, while remaining agnostic to any specific features of a single protein sequence. Next, I will take a closer look at how a specific mutation to γD-crystallin, a structural protein of the eye lens implicated in cataract disease, affects topological properties of the aggregates that cause cataract. Finally, I show how the structures of 1250 variants of the SARS-CoV-2 Main Protease that were collected during the first year of the Covid-19 pandemic responded to evolutionary pressure with mutations that modify internal interactions between residues, altering the flexibility of the protein and its active site. Together, these analyses illustrate the effects of the multitude of interactions proteins experience on the resulting structure of proteins and protein aggregates.