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Free Energy Landscape of a Protein-Like Chain in a Fluid with Discontinuous Potentials

The free energy landscape of a protein-like chain in a fluid was studied by combining discontinuous molecular dynamics and parallel tempering. The model protein is a repeating sequence of four different beads, with interactions mimicking those in real proteins. Neighbor distances and angles are restricted to physical ranges and one out of the four kinds of beads can form hydrogen bonds with each other, except if they are too close in the chain. In contrast to earlier studies of this model, an explicit square-well solvent is included. Beads that can form intra-chain hydrogen bonds, can also form (weaker) hydrogen bonds with solvent molecules, while other beads are insoluble. By categorizing the protein configurations according to their intra-chain bonds, one can distinguish unfolded, helical, and collapsed helical structures. Simulations for chains of 15, 20 and 25 beads show that at low temperatures, the most likely structures are helical or collapsed helical, despite the low entropy of these structures. The temperature at which helical structures become dominant is higher than in the absence of a solvent. The cooperative effect of the solvent is attributed to the presence of hydrophobic beads. A phase transition of the solvent prevented the simulations of the 20-bead and 25-bead chains of reaching low enough temperatures to confirm whether the free energy landscape is funnel-shaped, although the results do not contradict that possibility.