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

Abstract

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 ~3.59 alpha-helix transforms to ~3.7 helix upon cooling below ~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 ~3.59-helix 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 ~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.