Abstract: Experiments only reveal a few of a protein’s structures with the atomic detail required to rationally engineer mutations and drugs. However, a protein actually has a vast landscape of uncharted conformations that present untapped opportunities for manipulating its function. My lab is developing simulation methods, called Markov state models (MSMs), that provide unprecedented access to proteins’ energy landscapes. We are employing these methods to understand how proteins function, to identify “cryptic” drug binding sites, and to design new drugs and proteins. Importantly, we have also developed a suite of experimental techniques for testing our predictions. This highly general platform is enabling progress on numerous scientific fronts. This talk will focus on how we are using this platform to understand and combat viruses like SARS-CoV-2 and Ebola.