In this case, principal component analysis (PCA) vectors have been commonly used instead as CVs for BPTI. Another limitation of WE is that it cannot have CVs such as PCA vectors, which can only reliably be obtained from a long simulation. GaMD, Markov state models (MSMs), and other methods that are post-processed, constructed, and analyzed after a long simulation is run can have PCA vectors, time-structure based independent component analysis (tICA) vectors, and other dimensionality reduction vectors to describe the system. Nonetheless, WE can have non-differentiable CVs such as the number of hydrogen bonds, which can be helpful for many systems. In contrast, other methods such as metadynamics and adaptive biasing force (ABF) need differentiable CVs. Moreover, WE does not add any statistical bias to the system and is exact regardless of the parameters, 102 so it can reliably obtain the actual kinetics of the system. Since a long simulation is typically needed to get reasonable estimates of the kinetics, researchers have recently developed methods for WE to estimate the actual kinetics faster. If GaMD-WE is combined with these current methods, more improvements will be seen in obtaining thermodynamic and kinetic properties.