On the molecular understanding of protein stability in water in chemical chaperone and its intercalation to dna

Abstract

Protein and DNA are two very important macromolecules in living organisms Both have different kind of functions DNA encodes the genetic information whereas proteins catalyse the biological reaction To perform the biological function proteins have to be in a folded native state The conformational change or misfolding of protein causes disease in living organisms For example misfolding of prion protein causes neurodegenerative disease in all mammals Prion protein is a glycoprotein located at brain cell It has three helices and an anti parallel 946 sheet The cellular prion protein termed as PrPC converts to a toxic more 946 rich conformation PrPSc Various studies including experimental and computational have been performed to find the mechanism of prion protein conversion Yet the mechanism is unclear In this thesis we have used the molecular dynamic simulation with enhanced sampling techniques to understand the mechanism of full prion unfolding for the first time in molecular detail Our finding shows that the cellular prion protein is an intrinsically disordered protein and it is in a metastable state in which any small perturbation would lead to a more stable unfolded state As mention above protein conformational change would cause the fatal disease in living organisms The protein folding unfolding or conformational changes are extremely dependent on the environment of proteins It has been proposed that the inorganic salts e g Na2So4 CaCl2 perturb the protein folding unfolding Similarly isolated amino acids AA also act as chemical chaperones and perturb the folding and stability of the protein The unique feature of amino acids is that they can exist in zwitterion and this way they would interact with the positive ARG and LYS and negative ASP and GLU residues of a protein In this thesis we have investigated the effect of glycine and other AA on protein folding We have observed that this AA interact with the charged residues of the protein Moreover among these charged residues they preferentially