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Structural biology WikiPage Draft edit

History edit

In 1912, Max Von Laue directed X-Rays at crystallized copper sulfate generating a diffraction pattern. These experiments led to the development of X-Ray Crystallography, and its usage in exploring biological structures. In 1951, Rosalind Franklin and Maurice Wilkins used X-ray diffraction patterns to capture the first image of deoxyribonucleic acid (DNA). Francis Crick and James Watson 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.

Pepsin crystals were the first proteins to be crystallized for use in X-Ray diffraction, by Theodore Svedberg who received the 1962 Nobel Prize in Chemistry. The first tertiary protein structure, that of Myoglobin, was published in 1958 by John Kendrew. During this time, modeling of protein structures was done using balsa wood or wire models. With the invention of modeling software such as CCP4 in the late 1970's, modeling is now done with computer assistance.

In the late 1930s and early 1940s, the combination of work done by Isidor Rabi, Felix Bloch, and Edward Mills Purcill led to the development of nuclear magnetic resonance (NMR). Currently, solid-state NMR is widely used in the field of structural biology to determine the structure and dynamic nature of proteins (protein NMR).[1] In 1990, Richard Henderson produced the first three-dimensional, high resolution image of bacteriorhodopsin using cryogenic electron microscopy (cryo-EM).[2]

More recently, computational methods have been developed to model and study biological structures. For example, molecular dynamics (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.[3] Recently, protein structure prediction was significantly improved by a new machine learning method called AlphaFold[4]. Some claim that computational approaches are starting to lead the field of structural biology research.[5]

 
Simplified flowchart of how structural biology plays a role in drug discovery

Applications edit

Structural biologists have made significant contributions towards understanding the molecular components and mechanism underlying human diseases. For example, cryo-EM and ssNMR have been used to study the aggregation of amyloid fibrils, which are associated with Alzheimer's disease, Parkinson's disease, and type II diabetes.[6] In 2021, a new Alzheimer's disease treatment called aducanumab was released, which is the first drug to prevent amyloid aggregation associated with Alzheimer's disease. Other researchers have used structural biology to better understand cancer.[7] Structural biology is also an important component of drug discovery.[8] Scientists can identify targets using genomics, study those targets using structural biology, and develop drugs that are suited for those targets.


UPDATED VERSION:

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 Alzheimer's disease, Parkinson's disease, and type II diabetes.[9] In 2021, a new Alzheimer's disease treatment called aducanumab was released, which is the first drug to prevent amyloid aggregation associated with Alzheimer's disease. 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.[10]

Structural biology is also an important component of drug discovery.[11] Scientists can identify targets using genomics, study those targets using structural biology, and develop drugs that are suited for those targets. Specifically, ligand-NMR, mass spectrometry, and X-ray crystallography are commonly used techniques in the drug discovery process. For example, researchers have used structural biology to better understand Met, which is an important drug target for cancer.[12] Similar research has been conducted for HIV targets to treat people with AIDS.[11] Researchers are also developing new antimicrobials for mycobacterial infections using structure-driven drug discovery.[11]

Core References Assignment edit

Four References for Structural biology edit

Article #1: Advances in Structural Biology and the Application to Biological Filament Systems[13]

  • This article details a lot of interesting techniques to study structural biology, and they actually assemble a model for a protein to demonstrate the utility of the techniques.

Article #2: The birth of computational structural biology[14]

  • This article can help me add to the "History" section of the Wiki article and talk about how the field has evolved to have a very strong computational component.

Article #3: Highly accurate protein structure prediction with AlphaFold[15]

  • This 2021 article talks about a novel approach of predicting the protein structure from amino acid sequences using machine learning. Very cool!

Article #4: The Structural Biology of Protein Aggregation Diseases:  Fundamental Questions and Some Answers[16]

  • This article is by a famous structural biologist/neuroscientist called David Eisenberg. I am thinking about using some of his work (along with others) to create a new section of "Applications" for this Wiki page.

Wiki Editing Project Ideas: edit

These are three topics that have a lot of room for growth with minimal citations.

Option 1: Structural biology edit

Article #1: Advances in Structural Biology and the Application to Biological Filament Systems[13]

  • This article details a lot of interesting techniques to study structural biology, and they actually assemble a model for a protein to demonstrate the utility of the techniques.

Option 2: Biophysical chemistry edit

Article #2: Biophysical processes underlying cross-seeding in amyloid aggregation and implications in amyloid pathology[17]

  • This article is very specific, but I thought it would be interesting to add different areas of study for biophysical chemistry to the article.

Option 3: Virophysics edit

Article #3: Biophysical characterization of influenza A virions[18]

  • This is a cool article where they use biophysical techniques to look at virions. I'm pretty sure this is the purpose of virophysics and could be an interesting primary article to include if I choose this topic.
  1. ^ Wüthrich, Kurt (2001-11). "The way to NMR structures of proteins". Nature Structural Biology. 8 (11): 923–925. doi:10.1038/nsb1101-923. ISSN 1545-9985. {{cite journal}}: Check date values in: |date= (help)
  2. ^ Henderson, R.; Baldwin, J. M.; Ceska, T. A.; Zemlin, F.; Beckmann, E.; Downing, K. H. (1990-06-20). "Model for the structure of bacteriorhodopsin based on high-resolution electron cryo-microscopy". Journal of Molecular Biology. 213 (4): 899–929. doi:10.1016/S0022-2836(05)80271-2. ISSN 0022-2836.
  3. ^ Levitt, Michael; Warshel, Arieh (1975-02). "Computer simulation of protein folding". Nature. 253 (5494): 694–698. doi:10.1038/253694a0. ISSN 0028-0836. {{cite journal}}: Check date values in: |date= (help)
  4. ^ Jumper, John; Evans, Richard; Pritzel, Alexander; Green, Tim; Figurnov, Michael; Ronneberger, Olaf; Tunyasuvunakool, Kathryn; Bates, Russ; Žídek, Augustin; Potapenko, Anna; Bridgland, Alex (2021-08). "Highly accurate protein structure prediction with AlphaFold". Nature. 596 (7873): 583–589. doi:10.1038/s41586-021-03819-2. ISSN 1476-4687. PMC 8371605. PMID 34265844. {{cite journal}}: Check date values in: |date= (help)CS1 maint: PMC format (link)
  5. ^ Nussinov, Ruth; Tsai, Chung-Jung; Shehu, Amarda; Jang, Hyunbum (2019-02-12). "Computational Structural Biology: Successes, Future Directions, and Challenges". Molecules. 24 (3): 637. doi:10.3390/molecules24030637. ISSN 1420-3049. PMC 6384756. PMID 30759724.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  6. ^ Iadanza, Matthew G.; Jackson, Matthew P.; Hewitt, Eric W.; Ranson, Neil A.; Radford, Sheena E. (2018-12). "A new era for understanding amyloid structures and disease". Nature Reviews Molecular Cell Biology. 19 (12): 755–773. doi:10.1038/s41580-018-0060-8. ISSN 1471-0080. {{cite journal}}: Check date values in: |date= (help)
  7. ^ Wendt, K. Ulrich; Weiss, Manfred S.; Cramer, Patrick; Heinz, Dirk W. (2008-02). "Structures and diseases". Nature Structural & Molecular Biology. 15 (2): 117–120. doi:10.1038/nsmb0208-117. ISSN 1545-9985. PMC 7097323. PMID 18250627. {{cite journal}}: Check date values in: |date= (help)CS1 maint: PMC format (link)
  8. ^ Thomas, Sherine E.; Mendes, Vitor; Kim, So Yeon; Malhotra, Sony; Ochoa-Montaño, Bernardo; Blaszczyk, Michal; Blundell, Tom L. (2017-08-18). "Structural Biology and the Design of New Therapeutics: From HIV and Cancer to Mycobacterial Infections: A Paper Dedicated to John Kendrew". Journal of Molecular Biology. John Kendrew’s 100th Anniversary Special Edition. 429 (17): 2677–2693. doi:10.1016/j.jmb.2017.06.014. ISSN 0022-2836.
  9. ^ Iadanza MG, Jackson MP, Hewitt EW, Ranson NA, Radford SE (December 2018). "A new era for understanding amyloid structures and disease". Nature Reviews. Molecular Cell Biology. 19 (12): 755–773. doi:10.1038/s41580-018-0060-8. PMID 30237470. S2CID 52307956.
  10. ^ Fitzpatrick, Anthony W. P.; Falcon, Benjamin; He, Shaoda; Murzin, Alexey G.; Murshudov, Garib; Garringer, Holly J.; Crowther, R. Anthony; Ghetti, Bernardino; Goedert, Michel; Scheres, Sjors H. W. (2017-07-13). "Cryo-EM structures of tau filaments from Alzheimer's disease". Nature. 547 (7662): 185–190. doi:10.1038/nature23002. ISSN 1476-4687. PMC 5552202. PMID 28678775.
  11. ^ a b c Thomas SE, Mendes V, Kim SY, Malhotra S, Ochoa-Montaño B, Blaszczyk M, Blundell TL (August 2017). "Structural Biology and the Design of New Therapeutics: From HIV and Cancer to Mycobacterial Infections: A Paper Dedicated to John Kendrew". Journal of Molecular Biology. John Kendrew’s 100th Anniversary Special Edition. 429 (17): 2677–2693. doi:10.1016/j.jmb.2017.06.014. PMID 28648615.
  12. ^ Wendt KU, Weiss MS, Cramer P, Heinz DW (February 2008). "Structures and diseases". Nature Structural & Molecular Biology. 15 (2): 117–120. doi:10.1038/nsmb0208-117. PMC 7097323. PMID 18250627.
  13. ^ a b Popp, David; Koh, Fujiet; Scipion, Clement P. M.; Ghoshdastider, Umesh; Narita, Akihiro; Holmes, Kenneth C.; Robinson, Robert C. (2018-04). "Advances in Structural Biology and the Application to Biological Filament Systems". BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology. 40 (4): e1700213. doi:10.1002/bies.201700213. ISSN 1521-1878. PMID 29484695. {{cite journal}}: Check date values in: |date= (help)
  14. ^ Levitt, Michael (2001-05). "The birth of computational structural biology". Nature Structural Biology. 8 (5): 392–393. doi:10.1038/87545. ISSN 1545-9985. {{cite journal}}: Check date values in: |date= (help)
  15. ^ Jumper, John; Evans, Richard; Pritzel, Alexander; Green, Tim; Figurnov, Michael; Ronneberger, Olaf; Tunyasuvunakool, Kathryn; Bates, Russ; Žídek, Augustin; Potapenko, Anna; Bridgland, Alex (2021-08). "Highly accurate protein structure prediction with AlphaFold". Nature. 596 (7873): 583–589. doi:10.1038/s41586-021-03819-2. ISSN 1476-4687. {{cite journal}}: Check date values in: |date= (help)
  16. ^ Eisenberg, David; Nelson, Rebecca; Sawaya, Michael R.; Balbirnie, Melinda; Sambashivan, Shilpa; Ivanova, Magdalena I.; Madsen, Anders Ø.; Riekel, Christian (2006-09-01). "The Structural Biology of Protein Aggregation Diseases:  Fundamental Questions and Some Answers". Accounts of Chemical Research. 39 (9): 568–575. doi:10.1021/ar0500618. ISSN 0001-4842. PMC 3017558. PMID 16981672.{{cite journal}}: CS1 maint: PMC format (link)
  17. ^ Ivanova, Magdalena I.; Lin, Yuxi; Lee, Young-Ho; Zheng, Jie; Ramamoorthy, Ayyalusamy (2021-02). "Biophysical processes underlying cross-seeding in amyloid aggregation and implications in amyloid pathology". Biophysical Chemistry. 269: 106507. doi:10.1016/j.bpc.2020.106507. ISSN 1873-4200. PMID 33254009. {{cite journal}}: Check date values in: |date= (help)
  18. ^ Parupudi, Arun; Gruia, Flaviu; Korman, Samuel A.; Dragulin-Otto, Sonia; Sra, Kuldip; Remmele, Richard L.; Bee, Jared S. (2017-09). "Biophysical characterization of influenza A virions". Journal of Virological Methods. 247: 91–98. doi:10.1016/j.jviromet.2017.06.002. ISSN 1879-0984. PMID 28601563. {{cite journal}}: Check date values in: |date= (help)
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