PROTEIN THERMAL-STABILITY, HYDROGEN-BONDS, AND ION-PAIRS

Researchers in both academia and industry have expressed strong intere st in comprehending the mechanisms responsible for enhancing the therm ostability of proteins. Many and different structural principles have been postulated for the increased stability. Here, 16 families of prot eins with different thermal stability were theoretically examined by c omparing their respective fractional polar atom surface areas and the number and type of hydrogen bonds and salt links between explicit prot ein atoms. In over 80% of the families, correlations were found betwee n the thermostability of the familial members and an increase in the n umber of hydrogen bonds as well as an increase in the fractional polar surface which results in added hydrogen bonding density to water. Thu s increased hydrogen bonding may provide the most general explanation for thermal stability in proteins. The number of ion pairs was also fo und to increase with thermal stability in two-thirds of the families t ested; however, their rate of addition was only about one-sixth that f or internal hydrogen bonds amongst the-protein atoms. The preferred re sidue exchanges and surface atom types useful in engineering enhanced stability were also examined. (C) 1997 Academic Press Limited.