Ligand complex structures in protein crystallography

An introduction to the Proceedings of the 2016 CCP4 Study Weekend on protein-ligand complex structures.

Guidelines for the successful generation of protein–ligand complex crystals

This article aims to guide efforts in protein–ligand complex crystal structure generation, with special consideration of protein construct design, and summarizes different approaches to co-crystallization and crystal soaking. Common problems and pitfalls are highlighted.

Keep it together: restraints in crystallographic refinement of macromolecule–ligand complexes

An overview of the process of ligand restraint generation for macromolecular crystallographic refinement is given.

Validation and extraction of molecular-geometry information from small-molecule databases

The entries from a freely available small-molecule database, the Crystallography Open Database, have been validated and a reliable subset of molecules has been selected for the extraction of molecular-geometry information. The atom types and corresponding bond and angle classes derived from this database have been subjected to validation, the results of which are used by AceDRG in the derivation of new ligand descriptions.

AceDRG: a stereochemical description generator for ligands

The program AceDRG generates accurate stereochemical descriptions, and one or more conformations, of a given ligand. The program also analyses entries and extracts local environment-dependent atom types, bonds and angles from the Crystallography Open Database.

An editor for the generation and customization of geometry restraints

Obtaining a restraint dictionary for novel ligands or improving restraints for known ligands can require their manual modification. This can be tedious and error-prone. REEL is a restraints editor that provides quick, easy and accurate development, allowing global changes and fine-tuning of individual restraints.

Getting the chemistry right: protonation, tautomers and the importance of H atoms in biological chemistry

H atoms are `hard to see' in X-ray crystal structures of protein–ligand complexes. This paper discusses the problem of identifying the correct tautomeric form(s) of protein-bound ligands.

Combining X-ray and neutron crystallography with spectroscopy

The use of neutron crystallography and in situ spectroscopy to study enzyme mechanism is discussed.

Polder maps: improving OMIT maps by excluding bulk solvent

Residual OMIT maps can be improved by the selective exclusion of bulk solvent from the OMIT region.

Ligand fitting with CCP4

The process of ligand fitting with CCP4 is reviewed, including identifying ligand density in the map, ligand fitting, refinement and subsequent validation. Recent developments are discussed, and are illustrated using instructive examples demonstrating practical application.

Strategies for carbohydrate model building, refinement and validation

This article addresses many of the typical difficulties that a structural biologist may face when dealing with carbohydrates, with an emphasis on problem solving in the resolution range where X-ray crystallography and cryo-electron microscopy are expected to overlap in the next decade.

Glycoblocks: a schematic three-dimensional representation for glycans and their interactions

With structural glycoscience finally gaining popularity, the need for a clear way of depicting glycans and their interactions in three dimensions is more pressing than ever. Here the Glycoblocks representation is introduced, which combines a simplified bonding-network depiction with the familiar two-dimensional glycan notation brought into three-dimensions.