Editing Protein (section)

===Structure determination===

Discovering the tertiary structure of a protein, or the quaternary structure of its complexes, can provide important clues about how the protein performs its function and how it can be affected, i.e. in [[Drug design#Structure-based|drug design]]. As proteins are [[Diffraction-limited system|too small to be seen]] under a [[Optical microscope|light microscope]], other methods have to be employed to determine their structure. Common experimental methods include [[X-ray crystallography]] and [[protein NMR|NMR spectroscopy]], both of which can produce structural information at [[atom]]ic resolution. However, NMR experiments are able to provide information from which a subset of distances between pairs of atoms can be estimated, and the final possible conformations for a protein are determined by solving a [[distance geometry]] problem. [[Dual polarisation interferometry]] is a quantitative analytical method for measuring the overall [[protein conformation]] and [[conformational change]]s due to interactions or other stimulus. [[Circular dichroism]] is another laboratory technique for determining internal β-sheet / α-helical composition of proteins. [[Cryoelectron microscopy]] is used to produce lower-resolution structural information about very large protein complexes, including assembled [[virus]]es;<ref name = "Brandon_1999" />{{rp|340–41}} a variant known as [[electron crystallography]] can produce high-resolution information in some cases, especially for two-dimensional crystals of membrane proteins.<ref name=Gonen2005/> Solved structures are usually deposited in the [[Protein Data Bank]] (PDB), a freely available resource from which structural data about thousands of proteins can be obtained in the form of [[Cartesian coordinates]] for each atom in the protein.<ref name=Standley2008/>

Many more gene sequences are known than protein structures. Further, the set of solved structures is biased toward proteins that can be easily subjected to the conditions required in [[X-ray crystallography]], one of the major structure determination methods. In particular, globular proteins are comparatively easy to [[crystallize]] in preparation for X-ray crystallography. Membrane proteins and large protein complexes, by contrast, are difficult to crystallize and are underrepresented in the PDB.<ref name=Walian2004/> [[Structural genomics]] initiatives have attempted to remedy these deficiencies by systematically solving representative structures of major fold classes. [[Protein structure prediction]] methods attempt to provide a means of generating a plausible structure for proteins whose structures have not been experimentally determined.<ref name=Sleator2012/>