Is Theory Leading Neutron Diffraction in Macromolecular Solvent Networks?

Abstract

Standard crystallographic practice models electron scattering as a spherically symmetric phenomenon about atoms in the absence of any external effects. We have recently developed a polarizable atomic multipole refinement method for macromolecular crystallography that presents a significant improvement to the resultant information contained in an atomic model. We apply this method to high resolution lysozyme and trypsin data sets and validate its utility for precisely describing biomolecular electron density as indicated by a decrease in 5-6% in the R and Rfree values relative to the deposited values. The resultant models also illustrate the ability of force field electrostatics to orient water networks and catalytically relevant hydrogens that can be used to make predictions regarding active site function and activity. Finally, a DNA model generates the zig-zag spine pattern of hydrogen bonding in the minor groove without manual intervention. Comparison of the solvent networks with macromolecular neutron models suggest the hydrogen bonding patterns and distances generated by our protocol are more consistent with condensed phase measures and more likely to yield energetically favorable hydrogen bonds. The refinement technique proposed should be useful in applications to enzymology, drug design, and protein folding.View Large Image | View Hi-Res Image | Download PowerPoint Slide