To tackle this problem, an approach is to use Collective Variables (CV) and Molecular Dynamics simulations to evaluate the Free Energy Landscape (FEL), subsequently locate the TS, and obtain an MFEP. As this approach only requires gradient (force) calculations, low-frequency harmonic modes have no effect on evaluating MFEPs. Since reactive processes generally have an activation barrier height that is larger than k B T , enhanced sampling methods, including umbrella sampling, Metadynamics (MetaD), replica exchange and Integrated Temperature Sampling (ITS) are used to overcome the activation barrier via biassing the Potential Energy