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<h2 id="history">History</h2> <p>In 1912 <a href="/facts/Max_Von_Laue/DkRxRP03">Max Von Laue</a> directed X-rays at crystallized <a href="/facts/Copper_sulfate/pEWD4ujp">copper sulfate</a> generating a <a href="/facts/Diffraction/Mk80xXHT">diffraction pattern</a>.<a class="footnote-ref" id="fnref:7" href="#fn:7"><sup>7</sup></a> These experiments led to the development of <a href="/facts/X-ray_crystallography/WtI0F5DN">X-ray crystallography</a>, and its usage in exploring biological structures.<a class="footnote-ref" id="fnref:8" href="#fn:8"><sup>8</sup></a> In 1951, <a href="/facts/Rosalind_Franklin/RL6AYVPM">Rosalind Franklin</a> and <a href="/facts/Maurice_Wilkins/nT5vv4Tu">Maurice Wilkins</a> used X-ray diffraction patterns to capture the first image of deoxyribonucleic acid (DNA). <a href="/facts/Francis_Crick/AG05HNKI">Francis Crick</a> and <a href="/facts/James_Watson/TnXJ7GCp">James Watson</a> modeled the double helical structure of DNA using this same technique in 1953 and received the Nobel Prize in Medicine along with Wilkins in 1962.<a class="footnote-ref" id="fnref:9" href="#fn:9"><sup>9</sup></a> </p><p><a href="/facts/Pepsin/pELlV241">Pepsin</a> crystals were the first proteins to be crystallized for use in X-ray diffraction, by <a href="/facts/Theodor_Svedberg/l3WVhGjW">Theodore Svedberg</a> who received the 1962 Nobel Prize in Chemistry.<a class="footnote-ref" id="fnref:10" href="#fn:10"><sup>10</sup></a> The first <a href="/facts/Protein_tertiary_structure/1QJVj1V1">tertiary protein structure</a>, that of <a href="/facts/Myoglobin/n6h2yBCJ">myoglobin</a>, was published in 1958 by <a href="/facts/John_Kendrew/KwWW3Kul">John Kendrew</a>.<a class="footnote-ref" id="fnref:11" href="#fn:11"><sup>11</sup></a> During this time, modeling of protein structures was done using <a href="/facts/Ochroma/dRIILpVw">balsa wood</a> or <a href="/facts/Wire/yyy05H1S">wire</a> models.<a class="footnote-ref" id="fnref:12" href="#fn:12"><sup>12</sup></a> With the invention of modeling software such as <a href="/facts/Collaborative_Computational_Project_Number_4/HPlpvq8t">CCP4</a> in the late 1970s,<a class="footnote-ref" id="fnref:13" href="#fn:13"><sup>13</sup></a> modeling is now done with computer assistance. Recent developments in the field have included the generation of <a href="/facts/Free-electron_laser/ew2F96XV">X-ray free electron lasers</a>, allowing analysis of the dynamics and motion of biological molecules,<a class="footnote-ref" id="fnref:14" href="#fn:14"><sup>14</sup></a> and the use of structural biology in assisting <a href="/facts/Synthetic_biology/rHSNe8j3">synthetic biology</a>.<a class="footnote-ref" id="fnref:15" href="#fn:15"><sup>15</sup></a> </p><p>In the late 1930s and early 1940s, the combination of work done by <a href="/facts/Isidor_Rabi/hmEXNWEJ">Isidor Rabi</a>, <a href="/facts/Felix_Bloch/yrtqNe9a">Felix Bloch</a>, and <a href="/facts/Edward_Mills_Purcell/V9UC5ygc">Edward Mills Purcell</a> led to the development of nuclear magnetic resonance (NMR). Currently, <a href="/facts/Solid-state_nuclear_magnetic_resonance/cumWwN7Y">solid-state NMR</a> is widely used in the field of structural biology to determine the structure and dynamic nature of proteins (<a href="/facts/Nuclear_magnetic_resonance_spectroscopy_of_proteins/lCIXAFzQ">protein NMR</a>).<a class="footnote-ref" id="fnref:16" href="#fn:16"><sup>16</sup></a> </p><p>In 1990, Richard Henderson produced the first three-dimensional, high resolution image of bacteriorhodopsin using <a href="/facts/Cryogenic_electron_microscopy/Hjbcf4Ec">cryogenic electron microscopy</a> (cryo-EM).<a class="footnote-ref" id="fnref:17" href="#fn:17"><sup>17</sup></a> Since then, cryo-EM has emerged as an increasingly popular technique to determine three-dimensional, high resolution structures of biological images.<a class="footnote-ref" id="fnref:18" href="#fn:18"><sup>18</sup></a> </p><p>More recently, computational methods have been developed to model and study biological structures. For example, <a href="/facts/Molecular_dynamics/yR3DNt6U">molecular dynamics</a> (MD) is commonly used to analyze the dynamic movements of biological molecules. In 1975, the first simulation of a biological folding process using MD was published in Nature.<a class="footnote-ref" id="fnref:19" href="#fn:19"><sup>19</sup></a> Recently, <a href="/facts/Protein_structure_prediction/sj6AbLjI">protein structure prediction</a> was significantly improved by a new machine learning method called <a href="/facts/AlphaFold/DwBhppKC">AlphaFold</a>.<a class="footnote-ref" id="fnref:20" href="#fn:20"><sup>20</sup></a> Some claim that computational approaches are starting to lead the field of structural biology research.<a class="footnote-ref" id="fnref:21" href="#fn:21"><sup>21</sup></a> </p> <h2 id="techniques">Techniques</h2> <p><a href="/facts/Biomolecule/DGvFzN7R">Biomolecules</a> are too small to see in detail even with the most advanced light <a href="/facts/Microscope/ldJp0CI3">microscopes</a>. The methods that structural biologists use to determine their structures generally involve measurements on vast numbers of identical molecules at the same time. These methods include: </p> <ul><li><a href="/facts/Mass_spectrometry/RH5WBHJ2">Mass spectrometry</a></li> <li><a href="/facts/X-ray_crystallography/WtI0F5DN">Macromolecular crystallography</a></li> <li><a href="/facts/Neutron_diffraction/fYXAunDW">Neutron diffraction</a></li> <li><a href="/facts/Proteolysis/GtQdv6J7">Proteolysis</a></li> <li><a href="/facts/Nuclear_magnetic_resonance_spectroscopy_of_proteins/lCIXAFzQ">Nuclear magnetic resonance spectroscopy of proteins</a> (NMR)</li> <li><a href="/facts/Electron_paramagnetic_resonance/TDHV8c9e">Electron paramagnetic resonance</a> (EPR)</li> <li><a href="/facts/Cryo-electron_microscopy/Hjbcf4Ec">Cryogenic electron microscopy</a> (cryoEM)</li> <li><a href="/facts/Electron_crystallography/RIMzhXpa">Electron crystallography</a> and <a href="/facts/Microcrystal_electron_diffraction/oT5K9STf">microcrystal electron diffraction</a></li> <li><a href="/facts/Multiangle_light_scattering/2cL4M8Aw">Multiangle light scattering</a></li> <li><a href="/facts/Biological_small-angle_scattering/HsnHd9o9">Small angle scattering</a></li> <li><a href="/facts/Ultrafast_laser_spectroscopy/ghdK61hE">Ultrafast laser spectroscopy</a></li> <li><a href="/facts/Anisotropic_terahertz_microspectroscopy/uLHfpuyH">Anisotropic terahertz microspectroscopy</a></li> <li><a href="/facts/Two-dimensional_infrared_spectroscopy/l08Aolq0">Two-dimensional infrared spectroscopy</a></li> <li>Dual-polarization interferometry and <a href="/facts/Circular_dichroism/sMKgzpF2">circular dichroism</a></li></ul> <p>Most often researchers use them to study the "<a href="/facts/Native_state/uBHLassN">native states</a>" of macromolecules. But variations on these methods are also used to watch nascent or <a href="/facts/Denaturation_(biochemistry)/Eh1hc3Bg">denatured</a> molecules assume or reassume their native states. See <a href="/facts/Protein_folding/rf3nR2Y1">protein folding</a>. </p><p>A third approach that structural biologists take to understanding structure is <a href="/facts/Bioinformatics/D5x2L8ee">bioinformatics</a> to look for patterns among the diverse <a href="/facts/DNA_sequence/hsPsNCQW">sequences</a> that give rise to particular shapes. Researchers often can deduce aspects of the structure of <a href="/facts/Integral_membrane_protein/Vztpmlu1">integral membrane proteins</a> based on the <a href="/facts/Membrane_topology/F7XBdREl">membrane topology</a> predicted by <a href="/facts/Hydrophobicity_analysis/lGloJUzr">hydrophobicity analysis</a>. See <a href="/facts/Protein_structure_prediction/sj6AbLjI">protein structure prediction</a>. </p> <h2 id="applications">Applications</h2> <p>Structural biologists have made significant contributions towards understanding the molecular components and mechanisms underlying human diseases. For example, cryo-EM and ssNMR have been used to study the aggregation of amyloid fibrils, which are associated with <a href="/facts/Alzheimer%2527s_disease/w7Ad6tdg">Alzheimer's disease</a>, <a href="/facts/Parkinson%2527s_disease/xpekKj6x">Parkinson's disease</a>, and <a href="/facts/Type_2_diabetes/zCMXksmt">type II diabetes</a>.<a class="footnote-ref" id="fnref:22" href="#fn:22"><sup>22</sup></a> In addition to amyloid proteins, scientists have used cryo-EM to produce high resolution models of tau filaments in the brain of Alzheimer's patients which may help develop better treatments in the future.<a class="footnote-ref" id="fnref:23" href="#fn:23"><sup>23</sup></a> Structural biology tools can also be used to explain interactions between pathogens and hosts. For example, structural biology tools have enabled <a href="/facts/Virologist/doDESmsB">virologists</a> to understand how the <a href="/facts/HIV_envelope/VeNqBmy4">HIV envelope</a> allows the virus to evade human immune responses.<a class="footnote-ref" id="fnref:24" href="#fn:24"><sup>24</sup></a> </p><p>Structural biology is also an important component of <a href="/facts/Drug_discovery/LLdDNvjy">drug discovery</a>.<a class="footnote-ref" id="fnref:25" href="#fn:25"><sup>25</sup></a> Scientists can identify targets using genomics, study those targets using structural biology, and develop drugs that are suited for those targets. Specifically, ligand-<a href="/facts/Nuclear_magnetic_resonance/pGYAn9Bz">NMR</a>, <a href="/facts/Mass_spectrometry/RH5WBHJ2">mass spectrometry</a>, and <a href="/facts/X-ray_crystallography/WtI0F5DN">X-ray crystallography</a> are commonly used techniques in the drug discovery process. For example, researchers have used structural biology to better understand <a href="/facts/C-Met/6QH18YEd">Met</a>, a protein encoded by a protooncogene that is an important drug target in <a href="/facts/Cancer/PVW6n1D0">cancer</a>.<a class="footnote-ref" id="fnref:26" href="#fn:26"><sup>26</sup></a> Similar research has been conducted for <a href="/facts/HIV/ulY2rgzu">HIV</a> targets to treat people with <a href="/facts/HIV%2fAIDS/RqLIEMuJ">AIDS</a>.<a class="footnote-ref" id="fnref:27" href="#fn:27"><sup>27</sup></a> Researchers are also developing new antimicrobials for mycobacterial infections using structure-driven drug discovery.<a class="footnote-ref" id="fnref:28" href="#fn:28"><sup>28</sup></a> </p> <h2 id="see-also">See also</h2> <ul> <li>Biology portal</li></ul> <ul><li><a href="/facts/Primary_structure/VaN6MEYh">Primary structure</a></li> <li><a href="/facts/Secondary_structure/VaN6MEYh">Secondary structure</a></li> <li><a href="/facts/Tertiary_structure/VaN6MEYh">Tertiary structure</a></li> <li><a href="/facts/Quaternary_structure/VaN6MEYh">Quaternary structure</a></li> <li><a href="/facts/Structural_domain/oUpFcSsl">Structural domain</a></li> <li><a href="/facts/Structural_motif/g8EBDBGW">Structural motif</a></li> <li><a href="/facts/Protein_subunit/HhuET9UP">Protein subunit</a></li> <li><a href="/facts/Molecular_model/e9ETq017">Molecular model</a></li> <li><a href="/facts/Cooperativity/CjSM8H3C">Cooperativity</a></li> <li><a href="/facts/Chaperonin/Nssx5Grz">Chaperonin</a></li> <li><a href="/facts/Structural_genomics/njr8xKka">Structural genomics</a></li> <li><a href="/facts/Stereochemistry/XkcRVNwd">Stereochemistry</a></li> <li><a href="/facts/Resolution_(electron_density)/TU13jIqE">Resolution (electron density)</a></li> <li><a href="/facts/Proteopedia/C2LhX6kn">Proteopedia</a> The collaborative, 3D encyclopedia of proteins and other <a href="/facts/Molecules/N9ljSfFq">molecules</a>.</li> <li><a href="/facts/Protein_structure_prediction/sj6AbLjI">Protein structure prediction</a></li> <li><a href="/facts/SBGrid_Consortium/2r5FyNYf">SBGrid Consortium</a></li></ul> <h2 id="further-reading">Further reading</h2> <ul><li>Carugo, Oliviero; Djinović-Carugo, Kristina (29 June 2023). <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10337885">"Structural biology: A golden era"</a>. <i>PLOS Biology</i>. 21 (6): e3002187. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1371%2Fjournal.pbio.3002187">10.1371/journal.pbio.3002187</a>. <a href="/facts/PMC_(identifier)/dX1zMt71">PMC</a> <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10337885">10337885</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/37384774">37384774</a>.</li> <li>Curry, Stephen (3 July 2015). <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4697198">"Structural Biology: A Century-long Journey into an Unseen World"</a>. <i>Interdisciplinary Science Reviews</i>. 40 (3): 308–328. <a href="/facts/Bibcode_(identifier)/9HtdQSGB">Bibcode</a>:<a href="https://ui.adsabs.harvard.edu/abs/2015ISRv...40..308C">2015ISRv...40..308C</a>. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1179%2F0308018815Z.000000000120">10.1179/0308018815Z.000000000120</a>. <a href="/facts/PMC_(identifier)/dX1zMt71">PMC</a> <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4697198">4697198</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/26740732">26740732</a>.</li></ul> <h2 id="external-links">External links</h2> At <a href="/facts/Wikiversity/buV7CGAn">Wikiversity</a>, you can learn more and teach others about Structural biology at the Department of Structural biology <ul><li> Media related to Structural biology at Wikimedia Commons</li> <li><a href="http://www.nature.com/nsmb/"><i>Nature: Structural & Molecular Biology</i> magazine website</a></li> <li><a href="http://www.journals.elsevier.com/journal-of-structural-biology/">Journal of Structural Biology</a></li> <li><a href="http://biochemweb.fenteany.com/structural.shtml">Structural Biology - The Virtual Library of Biochemistry, Molecular Biology and Cell Biology</a></li> <li><a href="http://www.structuralbiology.eu"><i>Structural Biology in Europe</i></a></li> <li><a href="https://www.xtal.iqf.csic.es/Cristalografia/index-en.html">Learning Crystallography</a></li></ul> <h2 id="references">References</h2> <ol> <li id="fn:1"><p>Liljas, Anders (2009). "What is Structural Biology and When Did It Start". Textbook of Structural Biology. World Scientific. pp. 7–9. ISBN 978-981-277-207-7. <a href="978-981-277-207-7" target="_blank">978-981-277-207-7</a> <a href="#fnref:1" class="footnote-back-ref">↩</a></p></li> <li id="fn:2"><p>Curry, Stephen (3 July 2015). "Structural Biology: A Century-long Journey into an Unseen World". Interdisciplinary Science Reviews. 40 (3): 308–328. Bibcode:2015ISRv...40..308C. doi:10.1179/0308018815Z.000000000120. PMC 4697198. PMID 26740732. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4697198" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4697198</a> <a href="#fnref:2" class="footnote-back-ref">↩</a></p></li> <li id="fn:3"><p>Campbell, Iain D. (2013). "The evolution of protein NMR". 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