Automated identification of elemental ions in macromolecular crystal structures.

Nathaniel Echols,Thomas C Terwilliger,Pavel V Afonine,Jane S Richardson,Nader Morshed,Randy J Read,Airlie J Mccoy,Mitchell D Miller,Paul D Adams

doi:10.1107/s1399004714001308

Abstract

Many macromolecular model-building and refinement programs can automatically place solvent atoms in electron density at moderate-to-high resolution. This process frequently builds water molecules in place of elemental ions, the identification of which must be performed manually. The solvent-picking algorithms in phenix.refine have been extended to build common ions based on an analysis of the chemical environment as well as physical properties such as occupancy, B factor and anomalous scattering. The method is most effective for heavier elements such as calcium and zinc, for which a majority of sites can be placed with few false positives in a diverse test set of structures. At atomic resolution, it is observed that it can also be possible to identify tightly bound sodium and magnesium ions. A number of challenges that contribute to the difficulty of completely automating the process of structure completion are discussed.

Highlights

In addition to organic molecules, macromolecular crystals frequently contain ordered monoatomic ions
The small regulatory protein calmodulin binds four Ca2+ ions, which act as a switch for calmodulin binding to other proteins; we selected the highest resolution structure in the Protein Data Bank (PDB) (PDB entry 1exr; Wilson & Brunger, 2000)
The false-positive rate was extremely low, with only two spurious Ca atoms built in PDB entries 3dzz and 3m83 (Levisson et al, 2012)

Summary

Introduction

In addition to organic molecules, macromolecular crystals frequently contain ordered monoatomic ions. These ions often account for a nontrivial amount of the scattering density in the unit cell and are often physiologically relevant, aiding in catalysis and substrate binding as well as stabilizing protein folds (Glusker, 1991; Harding et al, 2010). They are common components in many crystallization solutions, often at high concentrations. Identification of the lighter elements such as sodium, magnesium or chlorine is problematic, especially

Methods

Results

Conclusion