| The reconstruction of free energy surfaces by means of standard Molecular Dynamics or Monte Carlo simulations is often limited due to the presence of high energy barriers or other sampling bottlenecks. Well-tempered metadynamics [Barducci et al., Phys. Rev. Lett.,100, 020603 (2008) ] is a powerful method for overcoming this limitation and determining the free-energy dependence on a selected number of collective variables using an adaptive bias. The capabilities of the algorithm can be furthermore extended by combining it with Replica Exchange method. The efficiency of such approach has been shown by reconstructing the folding landscape of different mutants of hPin1 WW domain which encompass various folding mechanisms. |
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