Thermal Stability of Hydrophobic Helical Oligomers: A Lattice Simulation Study in Explicit Water

We investigate the thermal stability of helical hydrophobic oligomers using a three-dimensional, water-explicit lattice model and the Wang–Landau Monte Carlo method. The degree of oligomer helicity is controlled by the parameter εmm < 0, which mimics monomer–monomer hydrogen bond interactions leading to the formation of helical turns in atomistic proteins. We vary |εmm| between 0 and 4.5 kcal/mol and therefore investigate systems ranging from flexible homopolymers (i.e., those with no secondary structure) to helical oligomers that are stable over a broad range of temperatures. We find that systems with |εmm| ≤ 2.0 kcal/mol exhibit a broad thermal unfolding transition at high temperature, leading to an ensemble of random coils. In contrast, the structure of conformations involved in a second, low-temperature, transition is strongly dependent on |εmm|. Weakly helical oligomers are observed when |εmm| ≤ 1.0 kcal/mol and exhibit a low-temperature, cold-unfolding-like transition to an ensemble of strongly water-penetrated globular conformations. For higher |εmm| (1.7 kcal/mol ≤ |εmm| ≤ 2.0 kcal/mol), cold unfolding is suppressed, and the low-temperature conformational transition becomes a “crystallization”, in which a “molten” helix is transformed into a defect-free helix. The molten helix preserves ≥50% of the helical contacts observed in the “crystal” at a lower temperature. When |εmm| = 4.5 kcal/mol, we find that conformational transitions are largely suppressed within the range of temperatures investigated.