New developments in crystallography: exploring its technology, methods and scope in the molecular biosciences

Abstract

Since the Protein Data Bank (PDB) was founded in 1971, there are now over 120,000 depositions, the majority of which are from X-ray crystallography and 90% of those made use of synchrotron beamlines. At the Cambridge Structure Database (CSD), founded in 1965, there are more than 800,000 'small molecule' crystal structure depositions and a very large number of those are relevant in the biosciences as ligands or cofactors. The technology for crystal structure analysis is still developing rapidly both at synchrotrons and in home labs. Determination of the details of the hydrogen atoms in biological macromolecules is well served using neutrons as probe. Large multi-macromolecular complexes cause major challenges to crystallization; electrons as probes offer unique advantages here. Methods developments naturally accompany technology change, mainly incremental but some, such as the tuneability, intensity and collimation of synchrotron radiation, have effected radical changes in capability of biological crystallography. In the past few years, the X-ray laser has taken X-ray crystallography measurement times into the femtosecond range. In terms of applications many new discoveries have been made in the molecular biosciences. The scope of crystallographic techniques is indeed very wide. As examples, new insights into chemical catalysis of enzymes and relating ligand bound structures to thermodynamics have been gained but predictive power is seen as not yet achieved. Metal complexes are also an emerging theme for biomedicine applications. Our studies of coloration of live and cooked lobsters proved to be an unexpected favourite with the public and schoolchildren. More generally, public understanding of the biosciences and crystallography's role within the field have been greatly enhanced by the United Nations International Year of Crystallography coordinated by the International Union of Crystallography. This topical review describes each of these areas along with illustrative results to document the scope of each methodology.

X-ray data processing

“…Globally, the first dedicated synchrotron light source was the SRS at Daresbury Laboratory in the U.K., where the production of X-rays (in particular) was the primary purpose of the instrument. This became available to users in 1981, and allowed the study of smaller samples and the collection of better data than previously, on wavelength tuneable beamlines [ 1 ]. Developments across the globe since then have given more intense and better focused X-rays allowing the analysis of crystals a few microns across, as well as the use of specific wavelengths to utilize effects arising from atomic X-ray absorption edges.…”

“…The vast majority of detailed 3D structural information that has been discovered about proteins has been from single crystal X-ray diffraction studies (‘X-ray crystallography’); a review in this journal noted recently that over 120000 molecular structures have been deposited into the Protein Data Bank since its establishment in 1971 [ 1 ].…”

Recent Progress in the Discovery and Development of 2-Nitroimidazooxazines and 6-Nitroimidazooxazoles to Treat Tuberculosis and Neglected Tropical Diseases

“…Previous attempts at this have been unsuccessful [ 111 ]. However, new technologies for protein production, x-ray crystallography with very small crystals and cryo electron microscopy are poised to overcome previous hurdles, and expand the impact of structural biology on drug discovery over the coming decade [ 112 ].…”

Hadoop Spark Based Hydrogen Bond Analysis Tool (H-BAT) for Molecular Dynamics Simulation Trajectory Data

“…The complete information about a molecule at a particular instance is denoted as a MODEL. Such information can be generated through biomolecular structure determining experimental methods such as Nuclear Magnetic Resonance spectroscopy, X-ray crystallography and cryo-electron microscopy[30]. This information about the molecule at multiple instances of time is obtained through computational methodologies such as molecular dynamics simulations.…”