Characterizing paths between sequence-defined folds

Extensive experimental work has provided examples of paths which jump between different folds with a single mutation in sequence. Such single-mutation paths have been observed both for RNA and for proteins. It remains an open question whether there exist general principles for identifying and constructing sharp paths between different folds. We will discuss our efforts to characterize the frequency of single-mutation paths in several different sequence-to-structure landscapes and systematically assess the contribution of epistasis in creating these paths.