Enhanced sampling has increased its importance in simulations of large-scale functional dynamics of proteins. "Multiscale enhanced sampling (MSES)" is an enhanced sampling method applicable to large protein systems, in which all-atom (MM) sampling is extended through a coupling with the accelerated dynamics of a coarse-grained (CG) model. Here, we show that the sampling efficiency of MSES can be further improved by using multiple CG copies instead of a single CG model and by introducing repulsive forces between the CG copies. An application to chignolin folding in explicit solvent has demonstrated a significant improvement in sampling efficiency due to the extension. (C) 2014 Elsevier B.V. All rights reserved.