In REST2 , parts of the potential-energy function are scaled down to accelerate transitions, instead of increasing the temperature of the whole system as in standard temperature REMD . Usually, the dihedral angle terms and intramolecular nonbonded interactions of the solute are scaled in REST2 by a factor λ, while the solute-solvent interactions are scaled by √ λ. Since only a small part of the system is biased, REST2 can enable stronger acceleration while retaining a reasonably high replica-exchange acceptance probability.