DescriptionLittle is known about the evolutionary pathways enabling a protein to change its function to changing environmental needs, especially in regards to metabolism and toxicity. Evolution simulations that explicitly model the three-dimensional interaction of mutated proteins with their targets is a new approach that complements the ongoing explosion of directed evolution experiments. In this project, the evolutionary dynamics of a lattice representation of antibiotic resistance protein (beta lactamase) is studied by enhanced-sampling folding-binding simulations for an initial protein undergoing selection-dependent mutation to bind a new antibiotic. The goals of this work are to understand the fundamental physical bottlenecks and dynamical behavior of protein evolution. Important questions include the extent of dominant pathways (convergent evolution) and phase transitions in evolutionary rates (punctuated equilibrium). These principals and their structural underpinnings can also be used to inform rational design of antibiotics that exploit bottlenecks in pathogen mutational response.
OrganizationUT Southwestern
DepartmentGreen Center for Systems Biology
Sponsor Campus GridOSG Connect
Principal Investigator
Milo Lin
Field Of ScienceBiophysics