Structural biology can help us to see some of the detail missing from this view and consequently is a powerful tool to unpick the intricate and exquisite choreography of life. For centuries, we have been able to visualise structures inside a cell, but even the most powerful microscopes are limited in the detail they provide, either by the sheer physical  boundaries of magnification, or because the samples themselves are not alive and working. Structural biology methods delve beneath these limits bringing molecules to life in 3D and into sharper focus. It reaches to the very limits of how a molecule works and how its function can be modified. The process of determining molecular structure can be long and frustrating – sometimes taking years. Mostly, proteins are the targets for structure analysis as these are the main ‘doing’ molecules of the cell.  Proteins are built from a DNA template and the string of amino acids thus synthesized fold into very complex loops, sheets and coils – it might seem like a tangle, but this structure dictates how the protein will interact with other structures around it in order to undertake its duties in the cell. The elegant structures of molecules and the complexes they form can be breathtaking in their logic and symmetry, but they are also supreme in helping us to understand how cells actually work. Suddenly shapes, sizes and assemblies of molecules can be assigned to various compartments in cells and put into context with their surrounding environment. A key aim of structural cell biology is to build a landscape representation of cellular function. The emergent picture will be akin to a sophisticated and dynamic metropolis where molecular relationships are forged and broken, short- or long-lived and all are shaped by the inevitability of cell reproduction, aging and death.

Chemical crystallography is a application of diffraction techniques to the study of structural chemistry. A frequent purpose is the identification of natural products, or of the products of synthetic chemistry experiments; however detailed molecular geometry, intermolecular interactions and absolute configurations can also be studied. Structures can be studied as a function of temperature, pressure or the application of electromagnetic radiation, or magnetic or electric field: such studies comprises only small minority of the total. The use of single crystal X ray diffraction to determine the structure of a chemical compound has been historically classified as 'Chemical Crystallography'. The methodologies, the accuracy in experiments coupled with the modem computer gadgets and advances in technology makes this branch of science an unequivocal provider of accurate and precise measurements of molecular dimensions. Structure determination by powder diffraction, crystal engineering, charge density analysis and studies on molecules in excited states are the recent add-ons.

X-rays are used to investigate the structural properties of solids, liquids or gels. Photons interact with electrons, and provide information about the fluctuations of electronic densities in the matter. A typical experimental set-up is shown on Figure 1: a monochromatic beam of incident wave vector ki is selected and falls on the sample. The scattered intensity is collected as a function of the so-called scattering angle 2θ. Elastic interactions are characterized by zero energy transfers, such that the final wave vector kf is equal in modulus to ki. The scattered intensity I(q) is the Fourier Transform of g(r), the correlation function of the electronic density r(r), which corresponds to the probability to find a scatterer at position r in the sample if another scatterer is located at position 0 : elastic x-ray scattering experiments reveal the spatial correlations in the sample. Small angle scattering experiments are designed to measure I(q) at very small scattering vectors q»(4p/l)q, with 2q ranging from few micro-radians to a ten of radians, in order to investigate systems with characteristic sizes ranging from crystallographic distances (few Å) to colloidal sizes (up to few microns).

It should be clear that all matter is made of atoms. From the periodic table, it can be seen that there are only about 100 different kinds of atoms in the entire Universe. These same 100 atoms form thousands of different substances ranging from the air we breathe to the metal used to support tall buildings. Metals behave differently than ceramics, and ceramics behave differently than polymers. The properties of matter depend on which atoms are used and how they are bonded together.The structure of materials can be classified by the general magnitude of various features being considered. The three most common major classification of structural, listed generally in increasing size, are: Atomic structure, which includes features that cannot be seen, such as the types of bonding between the atoms, and the way the atoms are arranged. Microstructure, which includes features that can be seen using a microscope, but seldom with the naked eye. Macrostructure, which includes features that can be seen with the naked eye)

The atomic structure primarily affects the chemical, physical, thermal, electrical, magnetic, and optical properties. The microstructure and macrostructure can also affect these properties but they generally have a larger effect on mechanical properties and on the rate of chemical reaction. The properties of a material offer clues as to the structure of the material. The strength of metals suggests that these atoms are held together by strong bonds. However, these bonds must also allow atoms to move since metals are also usually formable. To understand the structure of a material, the type of atoms present, and how the atoms are arranged and bonded must be known. Let’s first look at atomic bonding.

X-ray free-electron lasers (XFELs) open up new possibilities for X-ray crystallographic and spectroscopic studies of radiation-sensitive biological samples under close to physiological conditions. To facilitate these new X-ray sources, tailored experimental methods and data-processing protocols have to be developed. The highly radiation-sensitive photosystem II (PSII) protein complex is a prime target for XFEL experiments aiming to study the mechanism of light-induced water oxidation taking place at a Mn cluster in this complex. We developed a set of tools for the study of PSII at XFELs, including a new liquid jet based on electrofocusing, an energy dispersive von Hamos X-ray emission spectrometer for the hard X-ray range and a high-throughput soft X-ray spectrometer based on a reflection zone plate. While our immediate focus is on PSII, the methods we describe here are applicable to a wide range of metalloenzymes. These experimental developments were complemented by a new software suite, cctbx.xfel. This software suite allows for near-real-time monitoring of the experimental parameters and detector signals and the detailed analysis of the diffraction and spectroscopy data collected by us at the Linac Coherent Light Source, taking into account the specific characteristics of data measured at an XFEL.

Crystallography technique has been a widely used tool for elucidation of compounds present in milk and other types of information obtained through structure function relationship. Although more detailed information from X-ray analysis has been secured from substances which are commonly known to be crystalline, it has been surprising to find substances commonly thought of as being non-crystalline as actually having a partially crystalline structure and that this structure can be changed by heat treatment, pressure, stretching, etc. Casein is an example of the latter class of proteins. Stewart has shown that even solutions tend to assume an orderly arrangement of groups within the solution. Hence, liquid milk should, and does show some type of arrangement. The mineral constituent and lactose are the only true crystalline constituents in dairy products that can be analyzed by X-ray; nevertheless, interesting structural changes have been observed in butterfat, milk powder, casein and cheese.