  Numerous studies have investigated the differences and similarities between
protein structures determined by solution NMR spectroscopy and those determined
by x-ray crystallography. A fundamental question is whether any observed
differences are due to differing methodologies, or to differences in the
behavior of proteins in solution versus in the crystalline state. Here, we
compare the properties of the hydrophobic cores of high-resolution protein
crystal structures and those in NMR structures, determined using increasing
numbers and types of restraints. Prior studies have reported that many NMR
structures have denser cores compared to those of high-resolution x-ray crystal
structures. Our current work investigates this result in more detail, and finds
that these NMR structures tend to violate basic features of protein
stereochemistry, such as small non-bonded atomic overlaps and few Ramachandran
and side chain dihedral angle outliers. We find that NMR structures solved with
more restraints, and which do not significantly violate stereochemistry, have
hydrophobic cores that have a similar size and packing fraction as their
counterparts determined by x-ray crystallography at high-resolution. These
results lead us to conclude that, at least regarding the core packing
properties, high-quality structures determined by NMR and x-ray crystallography
are the same, and the differences reported earlier are most likely a
consequence of methodology, rather than fundamental differences between the
protein in the two different environments.
