For 35 years, the prevailing view has been that the hydrophobic effect
is the dominant force in protein folding. The importance of hydrogen
bonding was always clear, but whether it made a net favorable contribu
tion to protein stability was not, Studies of mutant proteins have imp
roved our understanding of the forces stabilizing proteins. They sugge
st that hydrogen bonding and the hydrophobic effect make large but com
parable contributions to the stability of globular proteins.