The overarching goal of the Harms lab is to understand the relationship between the biophysical properties of proteins and their evolution. Why do proteins with certain sequences and physical properties—out of a huge space of possibilities—occur? How do the physical properties of proteins shape their evolutionary trajectories? Which protein features are optimized by evolution, and which are determined by chance? How does a blind evolutionary process assemble complex features like ligand binding sites or allosteric regulation? Is protein evolution predictable or stochastic? To answer these (and other) questions, we take a synthetic approach, combining concepts and methodologies from classical biophysics and evolutionary biology. We employ advanced phylogenetics techniques (including ancestral protein resurrection), high-throughput experimental screens, and rigorous experimental/computational biophysical approaches to directly study the interplay of evolutionary and biophysical forces in generating both the complexity and diversity of natural proteins.

  Biophysics of protein evolution