Figures and show the average free energy landscape (-k B T ln P , where P denotes probability) of chignolin after 500 ns of GaMD and WE, respectively. The lowest energy state was set to be zero for each free energy landscape. In particular, the GaMD run with the upper bound of the dihedral boost potential yielded the maximum number of initial structures on average as compared to the other five GaMD potential settings (see Supplementary Information). Cumulant expansion to the second order was used for GaMD reweighting. Although GaMD and WE have comparable free energy landscape coverage as seen in Figures and, GaMD has probabilities closer to actual values due to reweighting as seen in Figures and. This shows that it can still be more beneficial to use GaMD instead of WE to sample the free energy landscape as GaMD yields a more accurate free energy landscape. We also show that GaMD-WE can converge to the correct rate constants faster and more accurately than WE, more notably than in the alanine dipeptide case. Specifically, rate constants between the four regions of interest shown in Figures and were measured over simulation time. The folded region was defined to be 0.0 Å ≤ RMSD ≤ 1.0 Å, unfolded region was defined to be 4.0 Å ≤ RMSD, intermediate I region was defined to be 3.5 Å ≤ RMSD ≤ 4.5 Å, 4.5 Å ≤ R g ≤ 6.5 Å, and the intermediate II region was defined to be 6.0 Å ≤ RMSD ≤ 7.0 Å, 7.0 Å ≤ R g ≤ 8.0 Å. Initial structures for the three GaMD-WE runs were from one of the three GaMD runs with an upper bound of dihedral boost potential that yielded the largest number of initial structures. WE and brute force simulations used the same initial structure as the GaMD runs. Figures and show the evolution of rate constants over aggregate simulation time, and Table summarizes the final rate constants for brute force, WE, and GaMD-WE simulations after 40 µs of simulation time. The reference brute force simulation values were obtained from averaging all first passage times from five independent 8 µs runs and performing Bayesian bootstrapping for 95 % confidence intervals. The first 2 µs of simulation time was cut off in the rate constant calculation to eliminate initial structure bias for brute force, WE, and GaMD-WE simulations.