Secondary structure specific entropy change of a partially unfolded protein molecule

The conformational disorder of a protein in its partially unfolded molten globule (MG) form leads to an overall gain in the configurational entropy of the protein molecule. However, considering the differential degree of unfolding of different secondary structural segments of the protein, the entropy gained by them may be nonuniform. In this work, our attempt has been to explore whether any correlation exists between the degree of unfolding of different segments of a protein and their entropy gains. For that, we have carried out atomistic molecular dynamics simulations of the folded native and a partially unfolded structures of the protein villin headpiece subdomain or HP-36 in aqueous medium. It is found that among the three alpha-helical segments of the protein, the central alpha-helix (helix-2) underwent unfolding during the transition with a consequent entropy gain significantly higher than that of the other two helical segments. The calculations further revealed that the differential entropy gain by the segments of a protein can be used as an effective measure to identify the unfolded segments of the protein and hence to explore the folding pathways.