Macromolecular recognition in the Protein Data Bank

X-ray structures in the PDB illustrate both the specific recognition of two polypeptide chains in protein–protein complexes and dimeric proteins and their nonspecific interaction at crystal contacts.

From structure of the complex to understanding of the biology

The most extensive structural information on viruses relates to apparently icosahedral virions and is based on X-ray crystallography and on cryo-electron microscopy single-particle reconstructions. This paper concerns itself with the study of the macromolecular complexes that constitute viruses, using structural hybrid techniques.

So how do you know you have a macromolecular complex?

Structures of protein complexes offer some of the most interesting insights into biological processes. In this article, the methods required to show that the complex observed is the physiological one are investigated.

Measurement of the formation of complexes in tyrosine kinase-mediated signal transduction

The use of isothermal titration calorimetry (ITC) provides a full thermodynamic characterization of an interaction in one experiment. The determination of the affinity is an important value; however, the additional layer of information provided by the change in enthalpy and entropy can help in understanding the biology. This is demonstrated with respect to tyrosine kinase-mediated signal transduction.

Solving structures of protein complexes by molecular replacement with Phaser

Four case studies in using maximum-likelihood molecular replacement, as implemented in the program Phaser, to solve structures of protein complexes are described.

EMatch: an efficient method for aligning atomic resolution subunits into intermediate-resolution cryo-EM maps of large macromolecular assemblies

A method for detecting structural homologs of components in an intermediate resolution cryo-EM map and their spatial configuration is presented.

Computational analyses of the surface properties of protein–protein interfaces

This paper presents a survey of techniques that explore the surface properties of protein:protein interfaces so as to inform the prediction of probable sites of protein:protein interaction on newly determined protein structures.

An introduction to stereochemical restraints

A brief summary of the types of restraint defined in refinement dictionaries.

The use of biophysical methods increases success in obtaining liganded crystal structures

This paper highlights some of the problems that can arise when attempting to obtain crystal structures of small molecule–protein complexes and how biophysical methods can be used to define and overcome these problems. Many of the techniques mentioned are also applicable to the study of protein–protein complexes and mode-of-action analysis.

Crystallization of protein–ligand complexes

Methods presented for growing protein–ligand complexes fall into the categories of co-expression of the protein with the ligands of interest, use of the ligands during protein purification, cocrystallization and soaking the ligands into existing crystals.

Structural biology contributions to the discovery of drugs to treat chronic myelogenous leukaemia

A case study showing how the determination of multiple cocrystal structures of the protein tyrosine kinase c-Abl was used to support drug discovery, resulting in a compound effective in the treatment of chronic myelogenous leukaemia.

Crystallographic refinement of ligand complexes

Methods and resources for obtaining chemically plausible starting models and restraint sets for refinement of ligand complexes are described and some of the potential pitfalls are discussed.

Ligand identification using electron-density map correlations

An automated ligand-fitting procedure is applied to (F_o − F_c)exp(iφ_c) difference density for 200 commonly found ligands from macromolecular structures in the Protein Data Bank to identify ligands from density maps.

Assessment of automatic ligand building in ARP/wARP

The performance of the ligand-building module of the ARP/wARP software suite is assessed through a large-scale test on known protein–ligand complexes. The results provide a detailed benchmark and guidelines for future improvements.