title: The biological function of an insect antifreeze protein simulated by molecular dynamics.
abstract: Antifreeze proteins (AFPs) protect certain cold-adapted organisms from freezing to death by selectively adsorbing to internal ice crystals and inhibiting ice propagation. The molecular details of AFP adsorption-inhibition is uncertain but is proposed to involve the Gibbs-Thomson effect. Here we show by using unbiased molecular dynamics simulations a protein structure-function mechanism for the spruce budworm Choristoneura fumiferana AFP, including stereo-specific binding and consequential melting and freezing inhibition. The protein binds indirectly to the prism ice face through a linear array of ordered water molecules that are structurally distinct from the ice. Mutation of the ice binding surface disrupts water-ordering and abolishes activity. The adsorption is virtually irreversible, and we confirm the ice growth inhibition is consistent with the Gibbs-Thomson law.
authors.affiliation: Victorian Life Sciences Computation Initiative, The University of Melbourne, Carlton, Australia.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Kuiper
authors.affiliation: ACRF Rational Drug Discovery Centre, St Vincent's Institute of Medical Research, Fitzroy, Australia.
authors.forename: Craig J
authors.initials: CJ
authors.lastname: Morton
authors.affiliation: School of Chemistry, The University of Melbourne, Melbourne, Australia.
authors.forename: Sneha E
authors.initials: SE
authors.lastname: Abraham
authors.affiliation: School of Chemistry, The University of Melbourne, Melbourne, Australia.
authors.forename: Angus
authors.initials: A
authors.lastname: Gray-Weale
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D021301:Antifreeze Proteins / Q000737:chemistry* / Q000235:genetics; D001665:Binding Sites; D003080:Cold Temperature; D003460:Crystallization; D005615:Freezing; D006860:Hydrogen Bonding; D007053:Ice / Q000032:analysis*; D019476:Insect Proteins / Q000737:chemistry* / Q000235:genetics; D007700:Kinetics; D007915:Lepidoptera / Q000737:chemistry* / Q000502:physiology; D056004:Molecular Dynamics Simulation; D009154:Mutation; D011485:Protein Binding; D013329:Structure-Activity Relationship; D013816:Thermodynamics; D013912:Threonine / Q000737:chemistry*
chemical_list: D021301:Antifreeze Proteins; D007053:Ice; D019476:Insect Proteins; D013912:Threonine
keywords: antifreeze proteins; biophysics; computational biology; crystallization inhibition; ice-binding; molecular dynamics; none; structural biology; systems biology; thermal hysteresis