Cold denaturation induced helix-to-helix transition and its implication to activity of helical antifreeze protein

Study of cold denaturation is relevant for understanding the freeze tolerant activity of organism at sub-zero environment. The proteins responsible for the survival of these organisms contain abundance of alpha-helix. Here we study the effect of cold temperature on the alpha-helical region of a widely used model system, Trp-cage miniprotein by means of extensive atomistic molecular dynamics simulations in conjunction with replica exchange scheme. We find a helix-to-helix transition when the usual similar to 3.59 alpha-helix transforms to similar to 3.7 helix upon cooling below similar to 230 K. This transition is primarily driven by enthalpy gain from water-water interactions with the significant enhancement of low-density liquid (LDL)-like water at cold temperature. Because the transition from similar to 3.59-helix to similar to 3.7-helix occurs at cold temperature, it may be accompanied by cold denaturation of protein. Like the cold denatured state of Trp-cage, type-1 antifreeze proteins (AFP) also have similar to 3.7 or more residues per helical turn. However, unlike Trp-cage, AFP has the 3.7-helix in its biological active form. Such helical arrangement in AFP facilitates the hydrogen bonding with the surrounding clathrate or ice-like water molecules, which is crucial for the antifreeze activity of AFP. (C) 2021 Elsevier B.V. All rights reserved.

Automated summary

The study examines the effect of cold temperature on the alpha-helical region of the Trp-cage miniprotein using molecular dynamics simulations, observing a helix-to-helix transition below 230K primarily driven by water-water interactions. This transition may lead to cold denaturation of the protein. Unlike Trp-cage, the antifreeze protein AFP has a helical arrangement that facilitates hydrogen bonding with surrounding ice-like water molecules, crucial for its antifreeze activity.