  Normal mode analysis offers an efficient way of modeling the conformational
flexibility of protein structures. Simple models defined by contact topology,
known as elastic network models, have been used to model a variety of systems,
but the validation is typically limited to individual modes for a single
protein. We use anisotropic displacement parameters from crystallography to
test the quality of prediction of both the magnitude and directionality of
conformational variance. Normal modes from four simple elastic network model
potentials and from the CHARMM forcefield are calculated for a data set of 83
diverse, ultrahigh resolution crystal structures. While all five potentials
provide good predictions of the magnitude of flexibility, the methods that
consider all atoms have a clear edge at prediction of directionality, and the
CHARMM potential produces the best agreement. The low-frequency modes from
different potentials are similar, but those computed from the CHARMM potential
show the greatest difference from the elastic network models. This was
illustrated by computing the dynamic correlation matrices from different
potentials for a PDZ domain structure. Comparison of normal mode results with
anisotropic temperature factors opens the possibility of using ultrahigh
resolution crystallographic data as a quantitative measure of molecular
flexibility. The comprehensive evaluation demonstrates the costs and benefits
of using normal mode potentials of varying complexity. Comparison of the
dynamic correlation matrices suggests that a combination of topological and
chemical potentials may help identify residues in which chemical forces make
large contributions to intramolecular coupling.
