A phenomenological description of the contributions of phonons to molecular
force is developed. It uses an approximation to consider macromolecules as
solid continua. The molecular modes of a molecule can then be characterize
d by a Debye-like description of the partition function. The resulting bimo
lecular interaction is a truly many-body force that is temperature dependen
t and can be of the order of 1 eV. These phonon forces depend on molecular
shape, composition, and density. They may therefore also be important for l
arge molecular conformational changes, including the unfolding of chain mol
ecules. For the later case, a significant change in zero-point energy is fo
und. This may be the underlying cause for cold denaturation of proteins. (C
) 2001 John Wiley & Sons, Inc.