The process of freezing proteins is widely used in applications ranging from processing and storage of biopharmaceuticals to cryo-EM analysis of protein complexes. The formation of an ice-water interface is a critical destabilization factor for the protein, which can be offset by the use of cryo-protectants. Using molecular dynamics simulation, we demonstrate that the presence of the ice-water interface leads to a lowering of the free-energy barrier for unfolding, resulting in rapid unfolding of the protein. The unfolding process does not require direct adsorption of the protein to the surface, but is rather mediated by nearby liquid molecules that show an increased tendency for hydrating nonpolar groups. The observed enhancement in the cold denaturation process upon ice formation can be mitigated by addition of glucose, which acts as a cryoprotectant through preferential exclusion from side chains of the protein.
Heightened cold-denaturation of proteins at the ice-water interface / Arsiccio, A.; McCarty, J.; Pisano, R.; Shea, J. -E.. - In: JOURNAL OF THE AMERICAN CHEMICAL SOCIETY. - ISSN 0002-7863. - 142:12(2020), pp. 5722-5730.
|Titolo:||Heightened cold-denaturation of proteins at the ice-water interface|
|Data di pubblicazione:||2020|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1021/jacs.9b13454|
|Appare nelle tipologie:||1.1 Articolo in rivista|