The small t 2 increase for Chignolin is unsurprising given the consistency of t 2 across the randomly sampled hyperparameter trials. However, the t 2 optimized MSM, model 3 (see Table and section S2. (see Table and section S2.4) shows the same unfolded-folded transition as model 1 (see Figure (c). Both the dual-objective optimizations (t 2 with t 2 /t 3 and the VAMP equivalent) increased both the t 2 and the separation of timescales (see Figure ).