To assess the performance of the DeepWEST approach with respect to WE and the hybrid GaMD-WE approach, we estimated the convergence of rate constants between metastable states, especially defined within folded and unfolded regions of chignolin (Table ). The Figure : Evolution of rate constants over aggregate simulation time for brute force simulation (black), WE simulations (red), GAMD-WE approach (blue), and DeepWEST approach (green). For WE, GaMD-WE, and the DeepWEST methods, the error bars represent 95% confidence intervals obtained from the standard deviation of three independent runs. two intermediate regions, I 1 and I 2 are separated apart in the PES, and convergence of rate constants between these regions is difficult to achieve. Figure demonstrates faster and more accurate convergence of the DeepWEST approach as compared to the WE and GaMD-WE approach for the transition from I 1 to I 2 . However, the GaMD-WE method outperformed the DeepWEST method in estimating the rate constant for the transition from I 2 to I 1 (Figure ). The DeepWEST method showed faster convergence and greater accuracy in estimating the rate constants between the I 2 and the folded states (Figure and 11f). Faster convergence for the DeepWEST method was also observed from the folded to the unfolded state (Figure ). However, the GaMD-WE and the DeepWEST method equally outperformed the WE method in estimating the rate constant in the transition from the unfolded to the folded state (Figure ). In conclusion, for all the cases, both the hybrid methods, especially the DeepWEST method, outperformed the WE method in achieving faster convergence and accuracy of rate constants between the metastable regions of interest.