posted on 2020-03-16, 15:28authored byAndrea Arsiccio, James McCarty, Roberto Pisano, Joan-Emma Shea
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.