  Torsional-space Monte Carlo simulations of flexible molecules are usually
based on the assumption that all values of dihedral angles have equal
probability in the absence of atomic interactions. In the present paper it is
shown that this assumption is not valid. Thermodynamic sampling using dihedral
angles or other internal coordinates has to account for both the correct metric
in conformational space and the conformation-dependence of the moment of
inertia tensor. Metric and moment of inertia terms appear as
conformation-dependent factors in the partition function and are obtained by
proper separation of internal and rotational degrees of freedom. The importance
of both factors is discussed for a number of short peptides as well as for the
folded and unfolded states of a protein. It is concluded that thermodynamic
Monte Carlo simulations of protein folding that neglect these correction
factors tend to underestimate the stability of the folded state.
