We apply this approach to three model systems, studied by conventional EVB simulations in our prior work, triosephosphate isomerase from Saccharomyces cerevisiae (yTPI) , PriA from Mycobacterium tuberculosis (MtPriA) , and protein tyrosine phosphatase 1B (PTP1B) , and demonstrate that this REMD-EVB framework significantly enhances conformational sampling while reducing computational cost (compared to the need to run a substantially larger number of replicas). Q-RepEx thus provides a useful tool for studies of chemical reactions in complex systems with significant conformational fluctuations along the chemical reaction coordinate, where substantial conformational sampling is critical.