Editing Protein folding (section)

===X-ray crystallography===
[[File:X ray diffraction.png|thumb|Steps of [[X-ray crystallography]]|321x321px]]
[[X-ray crystallography]] is one of the more efficient and important methods for attempting to decipher the three dimensional configuration of a folded protein.<ref name="Cowtan_2001">{{cite encyclopedia | url = http://people.bu.edu/mfk/restricted566/phaseproblem.pdf | title = Phase Problem in X-ray Crystallography, and Its Solution | last = Cowtan | first = Kevin | name-list-style = vanc | date = 2001 | encyclopedia = Encyclopedia of Life Sciences |publisher=Macmillan Publishers Ltd, Nature Publishing Group|access-date=November 3, 2016}}</ref> To be able to conduct X-ray crystallography, the protein under investigation must be located inside a crystal lattice. To place a protein inside a crystal lattice, one must have a suitable solvent for crystallization, obtain a pure protein at supersaturated levels in solution, and precipitate the crystals in solution.<ref>{{cite book | url=https://books.google.com/books?id=Jobr7svN0IIC&pg=PR5 |title = Principles of Protein X-Ray Crystallography | last = Drenth | first = Jan | name-list-style = vanc | date = 2007-04-05 | publisher = Springer Science & Business Media | isbn = 978-0-387-33746-3 }}</ref> Once a protein is crystallized, X-ray beams can be concentrated through the crystal lattice which would diffract the beams or shoot them outwards in various directions. These exiting beams are correlated to the specific three-dimensional configuration of the protein enclosed within. The X-rays specifically interact with the electron clouds surrounding the individual atoms within the protein crystal lattice and produce a discernible diffraction pattern.<ref name="Fersht_1999">{{cite book |url=https://books.google.com/books?id=QdpZz_ahA5UC&pg=PR20 |title=Structure and Mechanism in Protein Science: A Guide to Enzyme Catalysis and Protein Folding | last = Fersht | first = Alan | name-list-style = vanc | date = 1999 | publisher = Macmillan | isbn = 978-0-7167-3268-6 }}</ref> Only by relating the electron density clouds with the amplitude of the X-rays can this pattern be read and lead to assumptions of the phases or phase angles involved that complicate this method.<ref>{{cite journal |doi=10.1107/S0907444903017815 |title=The phase problem |journal=Acta Crystallographica Section D |volume=59 |issue=11 |pages=1881–90 |year=2003 |last1=Taylor |first1=Garry | name-list-style = vanc |pmid=14573942 |doi-access=free |bibcode=2003AcCrD..59.1881T }}</ref> Without the relation established through a mathematical basis known as [[Fourier transform]], the "[[phase problem]]" would render predicting the diffraction patterns very difficult.<ref name="Fersht_1999" /> Emerging methods like [[multiple isomorphous replacement]] use the presence of a heavy metal ion to diffract the X-rays into a more predictable manner, reducing the number of variables involved and resolving the phase problem.<ref name="Cowtan_2001" />