Elucidating the role of key structural motifs in antifreeze glycoproteins

Show simple item record

dc.contributor.author Pandey, Poonam
dc.contributor.author Mallajosyula, Sairam S.
dc.date.accessioned 2019-06-19T11:12:55Z
dc.date.available 2019-06-19T11:12:55Z
dc.date.issued 2019
dc.identifier.citation Pandey, Poonam and Mallajosyula, Sairam S., "Elucidating the role of key structural motifs in antifreeze glycoproteins", Physical Chemistry Chemical Physics, DOI: 10.1039/C8CP06743K, 2019. en_US
dc.identifier.uri https://doi.org/10.1039/C8CP06743K
dc.identifier.uri https://repository.iitgn.ac.in/handle/123456789/4475
dc.description.abstract Antifreeze glycoproteins (AFGPs) are distinctively riveting class of bio-macromolecules, which endows the survival of organisms inhabiting polar and subpolar regions. These proteins are supposed to hinder the microscopic freezing by interacting with the embryonic ice crystals and precluding their further growth. The underlying molecular mechanism of AFGP binding to ice has remained elusive due to insufficient structural characterization, with conflicting hypothesis on the possible binding mode of AFGPs; either via the hydrophobic peptide backbone or via the hydrophilic carbohydrate side chains; when interacting with ice. Chemical synthesis has allowed researchers to accesses synthetic variants of natural AFGPs. These studies revealed that AFGPs exhibit huge variations in the thermal hysteresis and ice shaping behavior on slight structural variations especially to the carbohydrate side chains. Four key structural motifs were identified as crucial to AFGP activity; presence of threonine -methyl group, -glycosidic carbohydrate-protein linkage, acetylamide group (-NHCOCH3) at C2 position of the carbohydrate linked to protein and the presence of carbohydrate hydroxyl groups. In this study, we use Molecular dynamics (MD) simulations to probe the microscopic properties of water along these structural variations of AFGPs. We find that these variations primarily influence the conformation space of AFGPs and also crucially control their hydration dynamics. Owing to the disordered nature of AFGPs we use Markov-State modeling to identify conformational preferences for AFGPs. The simulations reveal the importance of steric bulk, intra-molecular carbohydrate-protein H-bonds and conformational preferences (?- vs ?- linkages) in controlling the spatial segregation of hydrophilic and hydrophobic regions of AFGPs. We hypothesize that the hydrophobic component of AFGPs is crucial to its binding to ice which determines the ice shaping ability of AFGPs. However, the hydrophilic carbohydrate hydroxyl groups and their ability to form bridge waters control the subsequent hydration dynamics, which is key to the antifreeze properties. Investigating the tetrahedral order parameter of water molecules around the carbohydrates revealed a competition between solute and bulk influenced solvent structure, with maximum restructuring being observed in the interfacial region 2.5 � � 4.5 � away from the AFGPs.
dc.description.statementofresponsibility by Poonam Pandey� and��Sairam S Mallajosyula�
dc.language.iso en en_US
dc.publisher Royal Society of Chemistry en_US
dc.title Elucidating the role of key structural motifs in antifreeze glycoproteins en_US
dc.type Article en_US
dc.relation.journal Physical Chemistry Chemical Physics


Files in this item

Files Size Format View

There are no files associated with this item.

This item appears in the following Collection(s)

Show simple item record

Search Digital Repository


Browse

My Account