title: Thermal stability of hydrophobic helical oligomers: a lattice simulation study in explicit water.
abstract: 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.
authors.affiliation: Department of Chemical and Biological Engineering, Princeton University, Princeton, New Jersey 08544, USA. santiago.romero-vargas@yale.edu
authors.forename: Santiago
authors.initials: S
authors.lastname: Romero-Vargas Castrillón
authors.forename: Silvina
authors.initials: S
authors.lastname: Matysiak
authors.forename: Frank H
authors.initials: FH
authors.lastname: Stillinger
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Rossky
authors.forename: Pablo G
authors.initials: PG
authors.lastname: Debenedetti
mesh_terms: D000465:Algorithms; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D056004:Molecular Dynamics Simulation; D009010:Monte Carlo Method; D011108:Polymers / Q000737:chemistry*; D013696:Temperature; D014867:Water / Q000737:chemistry*
chemical_list: D011108:Polymers; D014867:Water