Presenter(s): Daria Wonderlick—Biochemistry
Faculty Mentor(s): Mike Harms
Session 5: The Bonds that Make Us
Designing better biomolecules is a long-standing goal for biochemists . Doing so requires a rigorous understanding of how the sequence of a biomolecule determines its properties . Sequence changes, known as mutations, alter these properties and drive the natural evolutionary process . If we can accurately predict how mutations impact biomolecular properties, we can engineer novel biomolecules for applications in medicine, energy, and technology . Predicting a mutational effect is challenging, however, because the effect often depends on the presence of other mutations . Previous work in the Harms lab suggests that some of these mutational interactions emerge from a thermodynamic property of biomolecules—the ensemble . A biomolecule’s ensemble is the collection of interchanging structures it can adopt . A mutation may impact any structure in the ensemble, and its effect arises from perturbations to the relative populations of these structures . Mutations will have different effects depending on the degree to which other mutations have redistributed the ensemble . To mechanistically understand how the ensemble mediates mutational interactions, I am characterizing the effects of five mutations alone and in combination on a magnesium- and adenine-binding RNA molecule with a simple four-structure ensemble . By measuring the amount of a fluorescent adenine analog bound in the presence of varying magnesium concentrations, I can detect the effect of mutations on each of the four structures in this ensemble . The simplicity of this system will provide detailed mechanistic insight into the relationship between ensembles and mutations that can be used to improve the mutational predictions required for successful biomolecule design .