Evolutionary walks on fitness landscapes: insights on adaptation and resistance

This lecture by Eugene Shakhnovich explores the concept of fitness landscapes in evolutionary biology, focusing on the biophysical fitness landscape of E. coli DHFR. The lecture covers topics such as the relationship between molecular properties and fitness, the impact of mutations on stability and activity, and the prediction of antibiotic resistance based on molecular properties. Shakhnovich discusses the evolutionary dynamics of resistance, the role of protein quality control in resistance, and the pleiotropic effects of mutations in DHFR. The lecture concludes with a discussion on the implications of mutations in DHFR at molecular, systems, and macroscopic levels.