Toward the physical basis of thermophilic proteins: linking of enriched polar interactions and reduced heat capacity of unfolding. Biophys

ABSTRACT The enrichment of salt bridges and hydrogen bonding in thermophilic proteins has long been recognized. Another tendency, featuring lower heat capacity of unfolding (Cp) than found in mesophilic proteins, is emerging from the recent literature. Here we present a simple electrostatic model to illustrate that formation of a salt-bridge or hydrogen-bonding network around an ionized group in the folded state leads to increased folding stability and decreased Cp. We thus suggest that the reduced Cp of thermophilic proteins could partly be attributed to enriched polar interactions. A reduced Cp might serve as an indicator for the contribution of polar interactions to folding stability