Role of medium- and long-range interactions to the stability of the mutants of T4 lysozyme

Inter-residue interactions play an important role to the folding and stabil ity of protein molecules. In this work, we analyze the role of medium- and long-range interactions to the stability of T4 lysozyme mutants. We found t hat, in buried mutations, the increase in long-range contacts upon mutation s destabilizes the protein, whereas, in surface mutations, the increase in long-range contacts increases the stability, indicating the importance of s urrounding polar residues to the stability of surface mutations. Further, t he increase in medium-range contacts decreases the stability of buried and surface mutations and a direct relationship is observed between the increas e of medium-range contacts and increase in stability for partially buried/e xposed mutations. Moreover, the relationship between amino acid properties and stability of T4 lysozyme mutants at positions Ile3, Phe53, and Leu99 sh owed that the effect of medium- and long-range contacts is less for buried mutations and the inter-residue contacts have significant correlation with the stability of partially buried mutations.