Importance of surrounding residues for protein stability of partially buried mutations

For understanding the factors influencing protein stability, we have analyz ed the relationship between changes in protein stability caused by partiall y buried mutations and changes in 48 physico-chemical, energetic and confor mational properties of amino acid residues. Multiple regression equations w ere derived to predict the stability of protein mutants and the efficiency of the method has been verified with both back-check and jack-knife tests. We observed a good agreement between experimental and computed stabilities. Further, we have analyzed the effect of sequence window length from 1 to 1 2 residues on each side of the mutated residue to include the sequence info rmation for predicting protein stability and we found that the preferred wi ndow length for obtaining the highest correlation is different for each sec ondary structure; the preferred window length for helical, strand and coil mutations are, respectively 0, 9 and 4 residues on both sides of the mutant residues. However, all the secondary structures have significant correlati on for a window length of one residue on each side of the mutant position, implying the role of short-range interactions. Extraction of surrounding re sidue information for various distances (3 to 20 Angstrom) around the mutan t position showed the highest correlation at 8 Angstrom, 6 Angstrom and 7 A ngstrom, respectively, for mutations in helical, strand and coil segments. Overall, the information about the surrounding residues within the sphere o f 7 to 8 Angstrom, may explain better the stability in all subsets of parti ally buried mutations implying that this distance is sufficient to accommod ate the residues influenced by major intramolecular interactions for the st ability of protein structures.