Important amino acid properties for enhanced thermostability from mesophilic to thermophilic proteins

Understanding the role of various interactions in enhancing the thermostabi lity of proteins is important not only for clarifying the mechanism of prot ein stability but also for designing stable proteins. In this work, we have analyzed the thermostability of 16 different families by comparing mesophi lic and thermophilic proteins with 48 various physicochemical, energetic an d conformational properties. We found that the increase in shape, s (locati on of branch point in side chain) increases the thermostability, whereas, a n opposite trend is observed for Gibbs free energy change of hydration for native proteins, G(hN), in 14 families. A good correlation is observed betw een these two properties and the simultaneous increases of -G(hN) and s is necessary to enhance the thermostability from mesophile to thermophile. The increase in shape, which tends to increase with increasing number of carbo n atoms both for polar and non-polar residues, may generate more packing an d compactness, and the position of beta and higher order branches may be im portant for better packing. On the other hand, the increase in -G(hN) in th ermophilic proteins increases the solubility of the proteins. This tendency counterbalances the increases in insolubility and unfolding heat capacity change due to the increase in the number of carbon atoms. Thus, the present results suggest that the stability of thermophilic proteins may be achieve d by a balance between better packing and solubility, (C) 1999 Elsevier Sci ence B.V. All rights reserved.