Structural analysis of Ca2+ dependent and Ca2+ independent type II antifreeze proteins: A comparative molecular dynamics simulation study

Comparative molecular dynamics simulations of Ca2+ dependent psychrophilic type II antifreeze protein (AFP) from herring (Clupea harengus) (hAFP) and Ca2+ independent type II antifreeze protein from long snout poacher (Brachyopsis rostratus) (lpAFP) have been performed for 10 ns each at five different temperatures. We have tried to investigate whether the Ca2+ dependent protein obtains any advantage in nature over the independent one. To this end the dynamic properties of these two proteins have been compared in terms of secondary structure content, molecular flexibility, solvent accessibility, intra molecular hydrogen bonds and protein–solvent interactions. At 298 and 373 K the flexibility of the Ca2+ independent molecule is higher which indicates that Ca2+ could contribute to stabilize the structure. The thermal unfolding pathways of the two proteins have also been monitored. The rate of unfolding is similar up to 373 K, beyond that hAFP shows faster unfolding than lpAFP. The essential subspaces explored by the simulations of hAFP and lpAFP at different temperatures are significantly different as revealed from principal component analysis. Our results may help in understanding the role of Ca2+ for hAFP to express antifreeze activity. Furthermore our study may also help in elucidating the molecular basis of thermostability of two structurally similar proteins, which perform the same function in different manner, one in presence of Ca2+, and the other in absence of the same.

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► MD simulation of Ca2+ dependent hAFP and independent lpAFP Type II AFPs is performed.
► In hAFP, Ca2+ coordination is maintained up to 373 K.
► Unfolding rate is similar up to 373 K, above hAFP shows faster unfolding than lpAFP.
► Up to 373 K lpAFP shows increased overall flexibility than hAFP.
► Essential subspaces of hAFP and lpAFP at different temperatures are non overlapping.