Imaging science in biochemistry

Research in biology aimed at understanding the fundamental processes of life and is both an experimental and an observational science. Over the course of the last century, all classes of biomolecules relevant to life have been discovered and defined. This article describes how protein structures are elucidated and represented. Biology progressed from cataloging of species and their life styles to analyzing their underlying molecular mechanisms. Among the molecules required by life, the proteins represent certainly the most fascinating class, as they are the actual “working molecules” involved both in the processes of life and the structure of the living beings. Proteins carry out diverse functions including signaling and chemical communication (e.g., kinases and hormones), structure (keratin and collagen), transport of metabolites (hemoglobin), and transformation of metabolites (enzymes). Observation and analysis, in contrast to modeling and simulation, are the main approaches used in biology. The development of microscopes permitted observation of the smaller members of the living kingdom and hence of the cells and the organelles they contain. However, observing macromolecules on an atomic level could not be achieved by visible light or electron microscopy. Recent advances allowed imaging of the outer shape of large molecular entities at low resolution. Consequently, indirect methods that reveal molecular organization in a crystal (x-ray crystallography) or interactions between atoms (NMR) have been developed and are routinely used. The reader has thus to keep in mind that all images are not direct observations. Images in this article were carefully selected to present a broad view of the various mode of representation used by scientists to help them unravel protein structure and function. Several programs to generate such images are available, and most of them are able to display or generate many of the different representations described in this article.