Core packing of well-defined x-ray and NMR structures is the same

TL;DR

This study compares the hydrophobic core packing of high-resolution NMR and x-ray protein structures, concluding that high-quality structures from both methods exhibit similar core packing properties, indicating methodology differences explain previous discrepancies.

Contribution

The paper demonstrates that when NMR structures meet stereochemical quality standards, their core packing is comparable to x-ray structures, clarifying the impact of structural quality on core properties.

Findings

High-quality NMR and x-ray structures have similar core packing fractions.

NMR structures with more restraints and better stereochemistry resemble x-ray structures.

Previous differences in core density are due to methodological artifacts, not fundamental structural differences.

Abstract

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.