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Although protein association often causes diseases like Alzheimer’s, Parkinson’s, Mad Cow etc., association of insulin into a hexameric arrangement leads to the formation of a robust oligomer that preserves the biologically active monomeric units in our body. Association of insulin monomers being a major pharmaceutical problem, the structural integrity of the hexamer incites special interest. Our investigations show that a team of 10 water molecules inside a cavity at the center of insulin hexamer significantly contributes to the stabilization of the unique structure of the biomolecular assembly. We also study the dissociation pathway of insulin dimer in pure water and in the presence of ethanol. The free energy landscape along the dissociation pathway shows rich structural diversity with a large barrier whose height is found to decrease with increase in ethanol concentration. |