Threading proteins at the speed limit of folding

Abstract

Mutations in proteins can speed-up folding/unfolding (1,2), by optimizing the population of intermediate states (3), by stabilizing transition states (1) or by tuning the ruggedness of the energy landscape (4). For fast folders, even the transition path time between states can be resolved (5). However, this process has yet to be fully resolved in single-molecule experiments (6). One way to quantify the ruggedness of a protein's energy landscape is to count the total number of conformational states of mutants (5).