Multicanonical Monte Carlo simulations of a de novo designed protein with end-to-end β-sheet

One of the smallest proteins with end-to-end β-sheet is the designed 36-residue protein DS119. We recently suggested that the rate-limiting step in the folding of the βαβ protein is the formation of the central helix that then provides a scaffold for the parallel β-sheet formed by the two chain ends. In the present report we investigate whether and how this folding mechanism depends on the energy function, and compare the efficiency of molecular dynamics and Monte Carlo implementations of multicanonical sampling. While we find the native structure with similar frequency as in our previous simulations, we observe that the folding mechanism differs for both force fields.