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Linus Pauling
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===Biological molecules=== [[File:Linus Pauling 1941.png|thumb|Pauling in 1941]] [[Image:Helix electron density myoglobin 2nrl 17-32.jpg|thumb|upright|An alpha helix in ultra-high-resolution electron density contours, with O atoms in red, N atoms in blue, and hydrogen bonds as green dotted lines (PDB file 2NRL, 17β32)]] In the mid-1930s, Pauling, strongly influenced by the biologically oriented funding priorities of the Rockefeller Foundation's [[Warren Weaver]], decided to strike out into new areas of interest.<ref name="Kay">{{Cite book |last=Kay |first=Lily E. |url=https://books.google.com/books?id=vEHeNI2a8OEC&pg=PA148 |title=The molecular vision of life: Caltech, the Rockefeller Foundation, and the rise of the new biology |date=1996 |publisher=Oxford University Press |isbn=978-0-19-511143-9 |location=New York [u.a.] |pages=148β151 |access-date=May 27, 2015}}</ref> Although Pauling's early interest had focused almost exclusively on inorganic molecular structures, he had occasionally thought about molecules of biological importance, in part because of Caltech's growing strength in biology. Pauling interacted with such great biologists as [[Thomas Hunt Morgan]], [[Theodosius Dobzhanski]], [[Calvin Bridges]] and [[Alfred Sturtevant]].<ref name="Califano">{{Cite book |last=Califano |first=Salvatore |url=https://books.google.com/books?id=s-sCt4RT0bMC&pg=PA198 |title=Pathways to modern chemical physics |date=2012 |publisher=Springer |isbn=978-3-642-28179-2 |location=Heidelberg [Germany] |page=198 |access-date=May 27, 2015}}</ref> His early work in this area included studies of the structure of [[hemoglobin]] with his student [[Charles D. Coryell]]. He demonstrated that the hemoglobin molecule changes structure when it gains or loses an [[oxygen]] molecule.<ref name=Califano/> As a result of this observation, he decided to conduct a more thorough study of [[protein structure]] in general. He returned to his earlier use of X-ray diffraction analysis. But protein structures were far less amenable to this technique than the crystalline minerals of his former work. The best X-ray pictures of proteins in the 1930s had been made by the British crystallographer [[William Astbury]], but when Pauling tried, in 1937, to account for Astbury's observations quantum mechanically, he could not.<ref name="Livio">{{Cite book |last=Livio |first=Mario |url=https://books.google.com/books?id=0XmmAwAAQBAJ&pg=PA285 |title=Brilliant blunders: from Darwin to Einstein: colossal mistakes by great scientists that changed our understanding of life and the universe |date=2014 |publisher=Simon & Schuster |isbn=978-1-4391-9237-5 |location=[S.l.]}}</ref> It took eleven years for Pauling to explain the problem: his [[mathematics|mathematical]] analysis was correct, but Astbury's pictures were taken in such a way that the protein molecules were tilted from their expected positions. Pauling had formulated a model for the structure of hemoglobin in which atoms were arranged in a [[helix|helical]] pattern, and applied this idea to proteins in general.{{citation needed|date=August 2023}} In 1951, based on the structures of [[amino acid]]s and [[peptide]]s and the planar nature of the [[peptide bond]], Pauling, [[Robert Corey]] and [[Herman Branson]] correctly proposed the [[alpha helix]] and [[beta sheet]] as the primary [[structural motif]]s in protein [[secondary structure]].<ref>{{Cite journal |last1=Pauling |first1=L |last2=Corey |first2=RB |year=1951 |title=Configurations of Polypeptide Chains With Favored Orientations Around Single Bonds: Two New Pleated Sheets |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=37 |issue=11 |pages=729β40 |bibcode=1951PNAS...37..729P |doi=10.1073/pnas.37.11.729 |pmc=1063460 |pmid=16578412 |doi-access=free}}</ref><ref name="Goertzel and Goertzel, p. 95-100">Goertzel and Goertzel, p. 95-100.</ref> This work exemplified Pauling's ability to think unconventionally; central to the structure was the unorthodox assumption that one turn of the helix may well contain a non-[[integer]] number of amino acid residues; for the alpha helix it is 3.7 amino acid residues per turn.{{citation needed|date=August 2023}} Pauling then proposed that [[deoxyribonucleic acid]] (DNA) was a [[triple helix]];<ref>{{Cite journal |last1=Pauling |first1=L |last2=Corey |first2=RB |date=February 1953 |title=A Proposed Structure For The Nucleic Acids |journal=Proc Natl Acad Sci U S A |volume=39 |issue=2 |pages=84β97 |bibcode=1953PNAS...39...84P |doi=10.1073/pnas.39.2.84 |pmc=1063734 |pmid=16578429 |doi-access=free}}</ref><ref>{{Cite web |title=Linus Pauling's DNA Model |url=http://www.farooqhussain.org/projects/paulingdnamodel |url-status=dead |archive-url=https://web.archive.org/web/20120204210701/http://www.farooqhussain.org/projects/paulingdnamodel |archive-date=February 4, 2012 |access-date=June 2, 2015}}</ref> his model contained several basic mistakes, including a proposal of neutral phosphate groups, an idea that conflicted with the acidity of DNA. [[William Lawrence Bragg|Sir Lawrence Bragg]] had been disappointed that Pauling had won the race to find the alpha [[Alpha helix|helix structure]] of proteins. Bragg's team had made a fundamental error in making their models of protein by not recognizing the planar nature of the peptide bond. When it was learned at the [[Cavendish Laboratory]] that Pauling was working on molecular models of the structure of DNA, [[James Watson]] and [[Francis Crick]] were allowed to make a molecular model of DNA. They later benefited from unpublished data from [[Maurice Wilkins]] and [[Rosalind Franklin]] at [[King's College London|King's College]] which showed evidence for a helix and planar base stacking along the helix axis. Early in 1953 Watson and Crick proposed a correct structure for the DNA double helix. Pauling later cited several reasons to explain how he had been misled about the structure of DNA, among them misleading density data and the lack of high quality X-ray diffraction photographs. Pauling described this situation as "the biggest disappointment in his life".<ref name="Dye-LATimes">{{Cite web |last=Dye |first=Lee |date=June 2, 1985 |title=The Deeply Personal War of Linus Pauling: Nobel Prize-Winning Chemist Still Battles for His Controversial Vitamin Theory |url=https://www.latimes.com/archives/la-xpm-1985-06-02-vw-15174-story.html |access-date=April 9, 2023 |website=[[Los Angeles Times]] |language=en-US}}</ref> During the time Pauling was researching the problem, Rosalind Franklin in England was creating the world's best images. They were key to Watson's and Crick's success. Pauling did not see them before devising his mistaken DNA structure, although his assistant Robert Corey did see at least some of them, while taking Pauling's place at a summer 1952 protein conference in England. Pauling had been prevented from attending because his passport was withheld by the State Department on suspicion that he had Communist sympathies. This led to the legend that Pauling missed the structure of DNA because of the politics of the day (this was at the start of the [[McCarthyism|McCarthy]] period in the United States). Politics did not play a critical role. Not only did Corey see the images at the time, but Pauling himself regained his passport within a few weeks and toured English laboratories well before writing his DNA paper. He had ample opportunity to visit Franklin's lab and see her work, but chose not to.<ref name="Nature" />{{rp|414β415}} Despite these times, Pauling chose to move on from them and be thankful for the discoveries that he had already found.<ref name="Dye-LATimes"/> Pauling also studied [[enzyme]] reactions and was among the first to point out that enzymes bring about reactions by stabilizing the [[transition state]] of the reaction, a view which is central to understanding their mechanism of action.<ref>{{Cite book |last=Metzler |first=David E. |url=https://books.google.com/books?id=X194AYXInC8C&pg=PA330 |title=Biochemistry |date=2003 |publisher=Harcourt, Academic Pr. |isbn=978-0-12-492541-0 |edition=2nd |location=San Diego |ref=Metzler}}</ref> He was also among the first scientists to postulate that the binding of [[antibodies]] to antigens would be due to a complementarity between their structures.<ref name="Lewis">{{Cite book |first1=Julius M. |last1=Cruse |first2=Robert E. |last2=Lewis |url=https://books.google.com/books?id=kNI5Lk2z37sC&pg=PA21 |title=Atlas of immunology |date=2010 |publisher=CRC Press/Taylor & Francis |isbn=978-1-4398-0268-7 |edition=3rd |location=Boca Raton, FL |page=21 |access-date=May 27, 2015}}</ref> Along the same lines, with the physicist turned biologist [[Max DelbrΓΌck]], he wrote an early paper arguing that [[DNA replication]] was likely to be due to [[Complementarity (molecular biology)|complementarity]], rather than similarity, as suggested by a few researchers. This was made clear in the model of the structure of DNA that Watson and Crick discovered.<ref name="Tudge">{{Cite book |last=Tudge |author-link=Colin Tudge |first=Colin |url=https://books.google.com/books?id=Wprqex2OGY4C&pg=PT74 |title=The engineer in the garden: Genes and genetics: from the idea of heredity to the creation of life |date=1995 |publisher=Hill and Wang |isbn=978-0-8090-4259-3 |edition=1st American |location=New York |access-date=May 27, 2015}}</ref>
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