Replica exchange molecular dynamics (REMD) simulation is a popular enhanced sampling method that is widely used for exploring the atomic mechanism of protein conformational change. However, the requirement of huge computational resources for REMD, especially with the explicit solvent model, largely limits its application. In this study, the availability and efficiency of a variant of velocity-scaling REMD (vsREMD) was assessed with adenylate kinase as an example. Although vsREMD achieved results consistent with those from conventional REMD and experimental studies, the number of replicas required for vsREMD (30) was much less than that for conventional REMD (80) to achieve a similar acceptance rate (∼0.2), demonstrating high efficiency of vsREMD to characterize the protein conformational change and associated free-energy profile. Thus, vsREMD is a highly efficient approach for studying the large-scale conformational change of protein systems.