To investigate whether GaMD-WE will be significantly more effective than WE for more complex systems, we tested the two methods on chignolin, a 138-atom system with ten residues (PDB: 1UAO). The modified Generalized Born implicit model with the model II radii was used to solvate the system implicitly. For GaMD-WE, GaMD was run for 500 ns, and WE was run for 39.5 µs so that the total simulation time amounted to 40 µs. Simulation time, τ for WE was set to 20 ps, equal to GaMD's sampling frequency. Target number of walkers per macrostate n w was set to 4. CVs were set to be the mass-weighted root-meansquare-deviation (RMSD) of C α atoms from the initial folded state (PDB: 1UAO) and the mass-weighted radius of gyration (R g ) of C α atoms. Macrostates were evenly spaced in intervals of 0.2 Å for both RMSD and R g (ranging from 0 Å to 8 Å).