Temperature-shuffled parallel cascade selection molecular dynamics accelerates the structural transitions of proteins.

Parallel cascade selection molecular dynamics (PaCS-MD) is an enhanced conformational sampling method for searching structural transition pathways from a given reactant to a product. Recently, a temperature-aided PaCS-MD (Vinod et al., Eur. Biophys. J. 2016, 45, 463) has been proposed as its extension, in which the temperatures were introduced as additional parameters in conformational resampling, whereas the temperature is fixed in the original PaCS-MD. In the present study, temperature-shuffled PaCS-MD is proposed as a further extension of temperature-aided PaCS-MD in which the temperatures are shuffled among different replicas at the beginning of each cycle of conformational resampling. To evaluate their conformational sampling efficiencies, the original, temperature-aided, and temperature-shuffled PaCS-MD were applied to a protein-folding process of Trp-cage, and their minimum computational costs to identify the native state were addressed. Through the evaluation, it was confirmed that temperature-shuffled PaCS-MD remarkably accelerated the protein-folding process of Trp-cage compared with the other methods. © 2017 Wiley Periodicals, Inc.