Molecular dynamics calculations provide a method
by which the dynamic properties of molecules can be explored
over timescales and at a level of detail that cannot be
obtained experimentally from NMR or X-ray analyses. Recent
work (Philippopoulos M, Mandel AM, Palmer AG III, Lim C,
1997, Proteins 28:481–493) has indicated
that the accuracy of these simulations is high, as measured
by the correspondence of parameters extracted from these
calculations to those determined through experimental means.
Here, we investigate the dynamic behavior of the Src homology
3 (SH3) domain of hematopoietic cell kinase (Hck) via 15N
backbone relaxation NMR studies and a set of four independent
4 ns solvated molecular dynamics calculations. We also
find that molecular dynamics simulations accurately reproduce
fast motion dynamics as estimated from generalized order
parameter (S2) analysis for regions
of the protein that have experimentally well-defined coordinates
(i.e., stable secondary structural elements). However,
for regions where the coordinates are not well defined,
as indicated by high local root-mean-square deviations
among NMR-determined structural family members or high
B-factors/low electron density in X-ray crystallography
determined structures, the parameters calculated from a
short to moderate length (less than 5–10 ns) molecular
dynamics trajectory are dependent on the particular coordinates
chosen as a starting point for the simulation.