Perturbation of long-range water dynamics as the mechanism for the antifreeze activity of antifreeze glycoprotein.

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TitlePerturbation of long-range water dynamics as the mechanism for the antifreeze activity of antifreeze glycoprotein.
Publication TypeJournal Article
Year of Publication2014
AuthorsMallajosyula, SS, Vanommeslaeghe, K, Mackerell, AD
JournalJ Phys Chem B
Volume118
Issue40
Pagination11696-706
Date Published2014 Oct 09
ISSN1520-5207
KeywordsAnimals, Antifreeze Proteins, Fish Proteins, Fishes, Hydrogen Bonding, Molecular Dynamics Simulation, Protein Conformation, Water
Abstract

Very little is known about the mechanism of antifreeze action of antifreeze glycoproteins (AFGPs) present in Antarctic teleost fish. Recent NMR and CD studies assisted with total synthesis of synthetic AFGP variants have provided insight into the structure of short AFGP glycopeptides, though the observations did not yield information on the antifreeze mechanism of action. In this study, we use Hamiltonian replica exchange (HREX) molecular dynamics simulations to probe the structure and surrounding aqueous environments of both the natural (AFGP8) and synthetic (s-AFGP4) AFGPs. AFGPs can adopt both amphiphilic and pseudoamphiphilic conformations, the preference of which is related to the proline content of the peptide. The arrangement of carbohydrates allows the hydroxyl groups on terminal galactose units to form stable water bridges which in turn influence the hydrogen-bond network, structure, and dynamics of the surrounding solvent. Interestingly, these local effects lead to the perturbation of the tetrahedral environment for water molecules in hydration layers far (10.0-12.0 Å) from the AFGPs. This structure-induced alteration of long-range hydration dynamics is proposed to be the major contributor to antifreeze activity, a conclusion that is in line with terahertz spectroscopy experiments. The detailed structure-mechanism correlation provided in this study could lead to the design of better synthetic AFGP variants.

DOI10.1021/jp508128d
Alternate JournalJ Phys Chem B
PubMed ID25137353
PubMed Central IDPMC4191590
Grant ListR01 GM070855 / GM / NIGMS NIH HHS / United States
GM070855 / GM / NIGMS NIH HHS / United States