To verify the robustness of our macrostate classifications, we performed a cross-validation analysis of macrostate populations using ∼50% bootstrapping of trajectory data over five trials (Figure ). The results show that average macrostate populations over sub-sampled datasets are comparable to the complete set, further suggesting macrostate assignments are robust. As a metric to evaluate the agreement with experimental NMR observables, we use the reduced χ 2 value, defined as χ 2 /N , where N = 158 is the number of experimental observables. χ 2 is defined as