X-ray crystallography has immensely contributed to the growth of the science of understanding the three-dimensional structure of matters. The atomic arrangement of small molecules such as salts, inorganic, organic complexes, and metallic compounds was determined. Later on, one after another flood of molecular structures from biological origins was solved using X-ray crystallography. The structure of DNA was determined using fiber diffraction methods in the 1950s, subsequently, structures of polysaccharides, fibrous proteins, and virion particles were determined. The crystal structures of the first protein molecules in the form of lysozyme, myoglobin, and hemoglobin were the enormous achievements of the 1960s, solved by single-crystal diffraction methods. Within a couple of decades later, atomic structures of viruses and membrane receptors were started to be determined. Currently, there are over 125 thousand crystal structures submitted to the PDB database at the rate of more than 3 thousand structures per year. In contrast, there are 12 thousand structures solved by NMR spectroscopy at the rate of just over 100 structures per year, whereas there are only 2 thousand structures available in PDB which are solved using computational methods. It shows the popularity of X-ray crystallography for revealing the atomic details of protein molecules in the field of structural biology. For determining the structure, the molecule is first crystallized to have a repetitive and regular arrangement of arrays in three-dimensional space. As the X-rays have a wavelength in the order of bond distances existing in matters, they are the suitable electromagnetic radiations to be used for finding detailed atomic positions. A beam of X-rays is diffracted from the crystalline matter and is collected at certain positions. The intensities, amplitude, and phases of the diffracted X-rays are convoluted to calculate the electron density of atoms in the crystal. The atomic positions are refined by putting them at mean positions in the electron density and eventually the atomic coordinates in 3-D space are revealed, which define the shape of the matter or a molecule. Biomolecular crystallography deals with the crystal structure determination of biomolecules such as proteins, nucleic acids, polysaccharides, complexes, etc. As the structure and the function of a biomolecule are closely associated, revealing the structure is incredibly advantageous in order to understand or alter the function of the biomolecules. This understanding has given rise to the advent of structure-based drug discovery methods. The available 3-D structure of a druggable target protein may also be used for structure-based drug design against a pathophysiological state.
Keywords: Biomolecules, Braggs law, Crystallization, Drug design, Diffraction, Phase problem, Structure factor, Three-dimensional Structure, X-ray scattering.