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

• Published in: The journal of physical chemistry. B 2012-08, Vol.116 (33), p.9963-9970
• Main Authors: Romero-Vargas Castrillón, Santiago, Matysiak, Silvina, Stillinger, Frank H, Rossky, Peter J, Debenedetti, Pablo G
• Format: Article
• Language: English
• Subjects: Algorithms; Computer simulation; Helical; Helicity; Hydrogen Bonding; Hydrophobic and Hydrophilic Interactions; Lattices; Molecular Dynamics Simulation; Monte Carlo Method; Oligomers; Polymers - chemistry; Preserves; Temperature; Thermal stability; Three dimensional models; Water - chemistry
• ISSN: 1520-6106; 1520-5207
• DOI: 10.1021/jp305134w

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 ε mm < 0, which mimics monomer–monomer hydrogen bond interactions leading to the formation of helical turns in atomistic proteins. We vary |ε mm | 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 |ε mm | ≤ 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 |ε mm |. Weakly helical oligomers are observed when |ε mm | ≤ 1.0 kcal/mol and exhibit a low-temperature, cold-unfolding-like transition to an ensemble of strongly water-penetrated globular conformations. For higher |ε mm | (1.7 kcal/mol ≤ |ε mm | ≤ 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 |ε mm | = 4.5 kcal/mol, we find that conformational transitions are largely suppressed within the range of temperatures investigated.