Structures, dynamics, and hydrogen-bond interactions of antifreeze proteins in TIP4P/Ice water and their dependence on force fields.

Hwankyu Lee,Jinkee Hong

doi:10.1371/journal.pone.0198887

Abstract

Tenebrio molitor antifreeze protein (TmAFP) was simulated with growing ice-water interfaces at a realistic melting temperature using TIP4P/Ice water model. To test compatibility of protein force fields (FFs) with TIP4P/Ice water, CHARMM, AMBER, and OPLS FFs were applied. CHARMM and AMBER FFs predict more β-sheet structure and lower diffusivity of TmAFP at the ice-water interface than does OPLS FF, indicating that β-sheet structure is important for the TmAFP-interface binding and antifreeze activity. In particular, CHARMM FF more clearly distinguishes the strengths of hydrogen bonds in the ice-binding and non-ice-binding sites of TmAFP than do other FFs, in agreement with experiments, implying that CHARMM FF can be a reasonable choice to simulate proteins with TIP4P/Ice water. Simulations of mutated TmAFPs show that for the same density of Thr residues, continuous arrangement of Thr with the distance of 0.4~0.6 nm induces the higher extent of antifreeze activity than does intermittent arrangement of Thr with larger distances. These findings suggest the choice of CHARMM FF for AFP-TIP4P/Ice simulations and help explain the relationship between Thr-residue arrangement and antifreeze activity.

Highlights

Antifreeze proteins (AFPs), which consist of polypeptides with various sizes and structures, are found in arctic or antarctic organisms such as bacteria [1], fungi [2], plants [3], insects [4], and fish [5,6,7] that can survive at temperatures even lower than -30 ̊C
To test the ability of different force fields (FFs) to predict the strength of hydrogen bonds between AFPs and TIP4P/Ice water, simulations of Tenebrio molitor antifreeze protein (TmAFP) with TIP4P/Ice water were performed using different FFs such as CHARMM, AMBER, and OPLS
Water molecules adjacent to the ice-binding site of TmAFP are highly ordered, indicating the binding between TmAFP and the ice-water interface, which is more significantly observed in CHARMM and AMBER FFs than in OPLS FF. This implies that CHARMM and AMBER FFs can more accurately reproduce the binding of TmAFP with the ice interface and its effect on the suppression of ice growth than does OPLS FF

Summary

Introduction

Antifreeze proteins (AFPs), which consist of polypeptides with various sizes and structures, are found in arctic or antarctic organisms such as bacteria [1], fungi [2], plants [3], insects [4], and fish [5,6,7] that can survive at temperatures even lower than -30 ̊C. AFPs have shown great potential for industrial applications such as cryopreservation [8], food processing [9], and hydrate inhibition [10], since they bind to specific planes of the growing ice crystal and inhibit ice growth, showing a noncolligative property [11,12,13], which can overcome the limitation of synthetic polymer-based antifreezes that typically require high concentrations. To increase the antifreeze efficiency of AFP, the structure of AFP and its interaction with specific ice plane need to be understood, which has motivated many experimental and theoretical studies. The DeVries group pioneered experimental and theoretical studies on the interactions between AFPs and ice-water interfaces.

Methods

Results

Conclusion