Role of weak interactions in thermal stability of proteins

A database analysis was done to study the role of weak interactions such as CH⋯O, CH⋯PI m and NH⋯PI m in the thermal stability of proteins. The CH⋯O and CH⋯PI m interactions are more in the case of thermophilic proteins as compared to mesophiles. Amino acid analysis showed that hydrophobic amino acids like Val and Ile, and Cys contribute more to CH⋯O hydrogen bonds where as Pro and Gly contribute more to CH⋯PI m interactions. Though NH⋯PI m interactions are dominated by Lys and Arg in thermophiles and mesophiles, the Arg contribution is significantly higher in thermophiles. Interestingly, Glycine is a predominant contributor to all the weak interactions. The number of aromatic amino acids in the thermophiles is more and hence a large number of aromatic clusters were observed in this class. Thus, a cumulative effect of weak interactions seems to be important in thermal stability of proteins. The study also shows that introduction of Gly, Arg, Phe, Pro, and Tyr may enhance the thermal stability.