The conformational stability of terminal helices of λ-repressor protein in aqueous dodine and choline-O-sulfate solutions.

In this article, we have ventured into the denaturation of fast folding λ-repressor protein at a millimolar concentration of dodine and henceforth, evaluated the candidature of choline-O-sulfate as a protecting osmolyte against it, employing classical molecular dynamics simulations. Our simulation results show that, the terminal helices of λ-repressor protein get unfolded in presence of ∼15 mM dodine while 0.5 M and higher concentration of COS can prevent this deleterious effect of dodine. Careful analyses of a set of simulations with increasing COS concentration reveals that a higher concentration of COS can provide remarkable stability to the protein, even slightly better than its native state in water. Different interaction parameters show that in aqueous dodine, both the dodinium and acetate ions interact strongly with the terminal helices to disrupt the structure whereas in presence of COS, due to the preferential interaction of COS with the protein molecule, dodine molecules get excluded from the protein surface. In addition, the favorable interaction of COS with dodinium head group, the dodinium ions become less available to the vicinity of protein surface which also plays an indirect but decisive role to prevent the unfolding of the terminal helical domains of the λ-repressor protein.