Three examples mentioned in the previous sections highlight how GaMD-WE can be more powerful than either GaMD or WE by itself. On the other hand, this hybrid method also reveals both methods' advantages and disadvantages. GaMD is more effective at sampling the configuration space than WE by being a CV-free method. By adding boost potentials to "fill" the energy wells in a CV-free manner, GaMD can sample the configuration space more evenly across different modes in the system. On the other hand, WE is mainly limited to efficiently sampling along the chosen CVs. This is not problematic if the chosen CVs sufficiently describe the dynamics of the system, but in most cases, it is difficult to know the best CVs a priori. In such cases, WE can be slow at sampling the configuration space with the orthogonal modes present. For alanine dipeptide and chignolin, chosen CVs have been commonly used in existing literatures. They are small enough systems for both GaMD and WE to sufficiently sample well. But for BPTI, the dihedral angles χ 1 -C14 and χ 1 -C38 are not commonly used CVs and have shown to be insufficient for WE to sample as effectively as GaMD. BPTI is also a much bigger system than alanine dipeptide or chignolin.