Cyrus Homi Chothia (19 February 1942 – 26 November 2019)[18] FRS[21][19] was an English biochemist who was an emeritus scientist at the Medical Research Council (MRC) Laboratory of Molecular Biology (LMB) at the University of Cambridge[22][23] and emeritus fellow of Wolfson College, Cambridge.[21][24][25][26][27][28][29]

Cyrus Chothia
Chothia in 2015
Born
Cyrus Homi Chothia

(1942-02-19)19 February 1942[18]
Died26 November 2019(2019-11-26) (aged 77)[19]
EducationAlleyn's School[20]
Alma mater
Awards
Scientific career
Institutions
Thesis[ProQuest 301370414 The crystal structures of some molecules active at cholinergic nerve receptors] (1973)
Doctoral advisorPeter J. Pauling[4]
Other academic advisorsMichael Levitt[5]
Frederic M. Richards[5]
Doctoral students
Other notable studentsArthur Lesk (postdoc)
Websitewww2.mrc-lmb.cam.ac.uk/group-leaders/emeritus/cyrus-chothia

Education

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Chothia was educated at Alleyn's School,[20] then went to study at Durham University graduating with a Bachelor of Science degree in 1965.[18] Chothia then completed a Master of Science degree at Birkbeck College in 1967 and a PhD from University College London[30] under the supervision of Peter Pauling [Wikidata],[31] the son of Linus Pauling.

Research and career

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After his PhD Chothia worked in the Laboratory of Molecular Biology (LMB) for three years. He then worked with Michael Levitt[5] at the Weizmann Institute of Science[32][33] followed by two years with Joel Janin at the Institut Pasteur in Paris.[34]

In 1976 Chothia returned to England to work at University College London and the LMB. With Arthur Lesk[3][35] he showed that proteins adapt to mutations by changes in structure.

In 1992 he proposed that most proteins are built of domains that come from a small number of families.[36] He collaborated with Alexey Murzin, Steven Brenner and Tim Hubbard to create the Structural Classification of Proteins database (SCOP),[37][38] a periodic table for all known protein structures. With Julian Gough[14] he created the Superfamily database[39] which uses Hidden Markov models to identify protein sequences that are related to those of known structures.

During his career, Chothia supervised 19 successful PhD students to completion[40] including Alex Bateman,[6] Steven E. Brenner,[10] Mark Bender Gerstein,[11] Julian Gough,[13] Sarah Teichmann,[15] Bissan Al-Lazikani,[41][42][43] Goga Apic,[44] Samantha Barré[citation needed][45] Matthew Bashton,[46][47][48][49] Dan Bolser,[50] Michael Bremang,[51] Bernard de Bono,[52][53] Emma Ganley (née Hill),[54][55][56] Martin Madera,[57][58] Siarhei Maslau,[59] Susan Miller,[60][61][62] Jong Park (aka Jong Bhak),[63][64][65] Rajkumar Sasidharan,[66][67] and Christine Vogel.[68][69]

Awards and honours

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Chothia was elected a Fellow of the Royal Society (FRS) in 2000.[18] His certificate of election and candidature reads:

Dr Chothia has shown how the amino sequences of proteins determine their structure, function and evolution. From an analysis of their structural regularities, he has developed a classification of protein structures that is now in general use. His picture of protein evolution suggests how proteins diverge and gain new functions. He has helped us to understand how their apparently limited set of slightly different structures allow immunoglobin to recognise an almost limitless variety of different antigens.[70]

In 2015, Chothia was elected a Fellow of the International Society for Computational Biology (ISCB)[71] and was awarded the ISCB Accomplishment by a Senior Scientist Award in honour of his work in using computational methods to understand protein structure.[1][72]

Alongside David Haussler and Michael Waterman, Chothia was awarded the 2015 Dan David Prize for his contributions to the field of bioinformatics.[2]

References

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  1. ^ a b "ISCB Cyrus Chothia, Curtis Huttenhower, and Larry Hunter Named 2015 ISCB Award Winners". Archived from the original on 11 February 2015.
  2. ^ a b "Wikipedia co-founder Jimmy Wales among 2015 Dan David Prize winners". Retrieved 13 February 2015.
  3. ^ a b Lesk, A.; Chothia, C. (1980). "How different amino acid sequences determine similar protein structures: The structure and evolutionary dynamics of the globins". Journal of Molecular Biology. 136 (3): 225–270. doi:10.1016/0022-2836(80)90373-3. PMID 7373651.
  4. ^ a b Cyrus Chothia at the Mathematics Genealogy Project
  5. ^ a b c "Cyrus H. Chothia, Chemistry Tree". Archived from the original on 27 February 2015.
  6. ^ a b Bateman, Alexander George (1997). Evolution of the structure and function of the immunoglobulin superfamily (PhD thesis). University of Cambridge.
  7. ^ "Dr Alex Bateman – Wellcome Trust Sanger Institute". Archived from the original on 7 February 2012.
  8. ^ Bateman, A; Eddy, S. R.; Chothia, C (1996). "Members of the immunoglobulin superfamily in bacteria". Protein Science. 5 (9): 1939–41. doi:10.1002/pro.5560050923. PMC 2143528. PMID 8880921.
  9. ^ Bateman, A; Chothia, C (1995). "Outline structures for the extracellular domains of the fibroblast growth factor receptors". Nature Structural Biology. 2 (12): 1068–74. doi:10.1038/nsb1295-1068. PMID 8846218. S2CID 20501031.
  10. ^ a b Brenner, Steven Elliot (1996). Molecular propinquity : evolutionary and structural relationships of proteins. lib.cam.ac.uk (PhD thesis). University of Cambridge. EThOS uk.bl.ethos.596888.
  11. ^ a b Gerstein, Mark Bender (1992). Protein recognition : surfaces and conformational change (PhD thesis). University of Cambridge.
  12. ^ Gerstein, M.; Chothia, C. (1991). "Analysis of protein loop closure. Two types of hinges produce one motion in lactate dehydrogenase". Journal of Molecular Biology. 220 (1): 133–149. doi:10.1016/0022-2836(91)90387-L. PMID 2067013.
  13. ^ a b Gough, Julian John Thurstan (2002). Hidden Markov models and their application to genome analysis in the context of protein structure (PDF) (PhD thesis). University of Cambridge. EThOS uk.bl.ethos.599547. Archived from the original (PDF) on 11 March 2015.
  14. ^ a b "Dr. Julian Gough's home page at the University of Bristol". Archived from the original on 25 March 2012.
  15. ^ a b Teichmann, Sarah Amalia (1999). Genome evolution : analysing proteomes with new methods (PhD thesis). University of Cambridge.
  16. ^ Park, J; Teichmann, S. A.; Hubbard, T; Chothia, C (1997). "Intermediate sequences increase the detection of homology between sequences". Journal of Molecular Biology. 273 (1): 349–54. doi:10.1006/jmbi.1997.1288. PMID 9367767.
  17. ^ Teichmann, S. A.; Park, J; Chothia, C (1998). "Structural assignments to the Mycoplasma genitalium proteins show extensive gene duplications and domain rearrangements". Proceedings of the National Academy of Sciences of the United States of America. 95 (25): 14658–63. Bibcode:1998PNAS...9514658T. doi:10.1073/pnas.95.25.14658. PMC 24505. PMID 9843945.  
  18. ^ a b c d Anon (2014). "Chothia, Cyrus Homi". Who's Who (online Oxford University Press ed.). A & C Black. doi:10.1093/ww/9780199540884.013.10866. (Subscription or UK public library membership required.)
  19. ^ a b "Cyrus Chothia (1942–2019)". 27 November 2019. Retrieved 27 November 2019.
  20. ^ a b "Dan David Prize Awarded to Dr Cyrus Chothia". Alleyn's School. Archived from the original on 23 March 2015.
  21. ^ a b "Wolfson College: Emeritus Fellow Dr Cyrus Chothia MA MSc FRS". Archived from the original on 5 February 2012.
  22. ^ "Cyrus Chothia: The protein origins of biological complexity, LMB Emeritus". Archived from the original on 15 February 2012.
  23. ^ "Structural genomics and protein structure". Mrc-lmb.cam.ac.uk. Archived from the original on 14 February 2015. Retrieved 24 June 2014.
  24. ^ Cyrus Chothia at DBLP Bibliography Server  
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  26. ^ Chothia, C.; Lesk, A. M.; Tramontano, A.; Levitt, M.; Smith-Gill, S. J.; Air, G.; Sheriff, S.; Padlan, E. A.; Davies, D.; Tulip, W. R.; Colman, P. M.; Spinelli, S.; Alzari, P. M.; Poljak, R. J. (1989). "Conformations of immunoglobulin hypervariable regions". Nature. 342 (6252): 877–883. Bibcode:1989Natur.342..877C. doi:10.1038/342877a0. PMID 2687698. S2CID 4241051.
  27. ^ Lewis, T. E.; Sillitoe, I; Andreeva, A; Blundell, T. L.; Buchan, D. W.; Chothia, C; Cozzetto, D; Dana, J. M.; Filippis, I; Gough, J; Jones, D. T.; Kelley, L. A.; Kleywegt, G. J.; Minneci, F; Mistry, J; Murzin, A. G.; Ochoa-Montaño, B; Oates, M. E.; Punta, M; Rackham, O. J.; Stahlhacke, J; Sternberg, M. J.; Velankar, S; Orengo, C (2015). "Genome3D: Exploiting structure to help users understand their sequences". Nucleic Acids Research. 43 (Database issue): D382–6. doi:10.1093/nar/gku973. PMC 4384030. PMID 25348407.
  28. ^ Chothia, C; Gough, J; Vogel, C; Teichmann, S. A. (2003). "Evolution of the protein repertoire". Science. 300 (5626): 1701–3. Bibcode:2003Sci...300.1701C. doi:10.1126/science.1085371. PMID 12805536. S2CID 27681885.
  29. ^ Cyrus Chothia's publications indexed by the Scopus bibliographic database. (subscription required)
  30. ^ Chothia, Cyrus (1973). The crystal structures of some molecules active at cholinergic nerve receptors (PhD thesis). University College London. OCLC 926297115. ProQuest 301370414.
  31. ^ Chothia, C.; Pauling, P. (1969). "On the conformations of hallucinogenic molecules and their correlation". Proceedings of the National Academy of Sciences of the United States of America. 63 (4): 1063–1070. Bibcode:1969PNAS...63.1063C. doi:10.1073/pnas.63.4.1063. PMC 223427. PMID 4311249.
  32. ^ Chothia, C.; Levitt, M.; Richardson, D. (1977). "Structure of proteins: Packing of alpha-helices and pleated sheets". Proceedings of the National Academy of Sciences of the United States of America. 74 (10): 4130–4134. Bibcode:1977PNAS...74.4130C. doi:10.1073/pnas.74.10.4130. PMC 431889. PMID 270659.
  33. ^ Levitt, M.; Chothia, C. (1976). "Structural patterns in globular proteins". Nature. 261 (5561): 552–558. Bibcode:1976Natur.261..552L. doi:10.1038/261552a0. PMID 934293. S2CID 4154884.
  34. ^ Sweet, R.; Wright, H.; Janin, J.; Chothia, C.; Blow, D. (1974). "Crystal structure of the complex of porcine trypsin with soybean trypsin inhibitor (Kunitz) at 2.6-A resolution". Biochemistry. 13 (20): 4212–4228. doi:10.1021/bi00717a024. PMID 4472048.
  35. ^ Lesk, A.; Chothia, C. (1980). "Solvent accessibility, protein surfaces, and protein folding". Biophysical Journal. 32 (1): 35–47. Bibcode:1980BpJ....32...35L. doi:10.1016/S0006-3495(80)84914-9. PMC 1327253. PMID 7248454.
  36. ^ Chothia, Cyrus (1992). "One thousand families for the molecular biologist". Nature. 357 (6379): 543–4. Bibcode:1992Natur.357..543C. doi:10.1038/357543a0. PMID 1608464. S2CID 4355476.
  37. ^ Hubbard, T.; Murzin, A.; Brenner, S.; Chothia, C. (1997). "SCOP: A structural classification of proteins database". Nucleic Acids Research. 25 (1): 236–239. doi:10.1093/nar/25.1.236. PMC 146380. PMID 9016544.
  38. ^ "UK government grants awarded to Cyrus Chothia". Research Councils UK. Archived from the original on 15 October 2014.
  39. ^ Gough, J.; Chothia, C. (2002). "SUPERFAMILY: HMMs representing all proteins of known structure. SCOP sequence searches, alignments and genome assignments". Nucleic Acids Research. 30 (1): 268–272. doi:10.1093/nar/30.1.268. PMC 99153. PMID 11752312.
  40. ^ Alex Bateman (2015). "Cyrus Chothia's academic family tree". twitter. Archived from the original on 15 July 2015.
  41. ^ Al-Lazikani, Bissan (1999). Canonical structures of immunoglobulins and T cell receptors (PhD thesis). University of Cambridge.
  42. ^ "Dr Bissan Al-Lazikani Team leader". The Institute of Cancer Research. Archived from the original on 5 March 2015.
  43. ^ Al-Lazikani, B; Lesk, A. M.; Chothia, C (2000). "Canonical structures for the hypervariable regions of T cell alphabeta receptors". Journal of Molecular Biology. 295 (4): 979–95. doi:10.1006/jmbi.1999.3358. PMID 10656805.
  44. ^ Apic, Gordana (2003). Evolution of multidomain proteins in genomes. lib.cam.ac.uk (PhD thesis). University of Cambridge. OCLC 894594841. EThOS uk.bl.ethos.619919.
  45. ^ Barré, Samantha; Greenberg, Andrew S.; Flajnik, Martin F.; Chothia, Cyrus (1994). "Structural conservation of hypervariable regions in immunoglobulins evolution". Nature Structural Biology. 1 (12): 915–920. doi:10.1038/nsb1294-915. PMID 7773781. S2CID 39728494.
  46. ^ Bashton, Matthew (2004). Functional analysis of domain combinations (PhD thesis). University of Cambridge.
  47. ^ "Dr Matthew Bashton: Research Associate: INSTINCT project". Archived from the original on 5 March 2015.
  48. ^ Bashton, M; Chothia, C (2002). "The geometry of domain combination in proteins". Journal of Molecular Biology. 315 (4): 927–39. doi:10.1006/jmbi.2001.5288. PMID 11812158.
  49. ^ Bashton, M; Chothia, C (2007). "The generation of new protein functions by the combination of domains". Structure. 15 (1): 85–99. doi:10.1016/j.str.2006.11.009. PMID 17223535.
  50. ^ Bolser, Daniel Murray (2007). The surfaces involved in the formation of protein complexes (PhD thesis). University of Cambridge.
  51. ^ Bremang, Michael Anthony (2012). The mouse protein repertoire : studies on alternative splicing, function and quality (PhD thesis). University of Cambridge.
  52. ^ de Bono, Bernard (2004). Immunoglobulin superfamily proteins in human and mouse (PhD thesis). University of Cambridge.
  53. ^ de Bono, B. (2003). "Exegesis: a procedure to improve gene predictions and its use to find immunoglobulin superfamily proteins in the human and mouse genomes". Nucleic Acids Research. 31 (21): 6096–6103. doi:10.1093/nar/gkg828. PMC 275470. PMID 14576296.
  54. ^ Hill, Emma Elizabeth (2002). Evolution of protein families: genome sequences and three dimensional structures (PhD thesis). University of Cambridge.
  55. ^ "Emma Hill's Homepage". University of California, Berkeley. Archived from the original on 13 July 2006.
  56. ^ "Emma Ganley (née Hill) PLOS staff". PLOS. Archived from the original on 24 April 2015.
  57. ^ Madera, Martin (2005). Hidden Markov models for detection of remote homology (PhD thesis). University of Cambridge.
  58. ^ Madera, M. (2004). "The SUPERFAMILY database in 2004: additions and improvements". Nucleic Acids Research. 32 (90001): 235D–239. doi:10.1093/nar/gkh117. PMC 308851. PMID 14681402.
  59. ^ Maslau, Siarhei (2007). Formation of the small molecule metabolism of Escherichia coli (PhD thesis). University of Cambridge.
  60. ^ Miller, G. S. P. (1987). Computer display and manufacture of 3-D models (PhD thesis). University of Cambridge. OCLC 59769936.
  61. ^ Miller, Susan; Janin, Joël; Lesk, Arthur M.; Chothia, Cyrus (1987). "Interior and surface of monomeric proteins". Journal of Molecular Biology. 196 (3): 641–656. doi:10.1016/0022-2836(87)90038-6. PMID 3681970.
  62. ^ Miller, Susan; Lesk, Arthur M.; Janin, Joël; Chothia, Cyrus (1987). "The accessible surface area and stability of oligomeric proteins". Nature. 328 (6133): 834–836. Bibcode:1987Natur.328..834M. doi:10.1038/328834a0. PMID 3627230. S2CID 4349684.
  63. ^ Park, Jong Hwa (1997). Genome sequence analysis and methods (PhD thesis). University of Cambridge.
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  65. ^ "Jong Bhak's home page: An entrepreneur and a scientist". jongbhak.com. Archived from the original on 20 December 2014.
  66. ^ Sasidharan, Rajkumar (2004). Protein evolution : the selection of acceptable mutations (PhD thesis). University of Cambridge.
  67. ^ Sasidharan, R.; Chothia, C. (2007). "The selection of acceptable protein mutations". Proceedings of the National Academy of Sciences. 104 (24): 10080–10085. Bibcode:2007PNAS..10410080S. doi:10.1073/pnas.0703737104. PMC 1891269. PMID 17540730.
  68. ^ Vogel, Christine (2004). A domain perspective on the evolution of the protein repertoire (PhD thesis). University of Cambridge.
  69. ^ Vogel, Christine; Chothia, Cyrus (2006). "Protein Family Expansions and Biological Complexity". PLOS Computational Biology. 2 (5): e48. Bibcode:2006PLSCB...2...48V. doi:10.1371/journal.pcbi.0020048. PMC 1464810. PMID 16733546.  
  70. ^ "EC/2000/04: Chothia, Cyrus". London: Royal Society. Archived from the original on 29 March 2022. Retrieved 18 November 2013.
  71. ^ Fogg, C. N.; Kovats, D. E. (2015). "Message from the ISCB: 2015 ISCB Accomplishment by a Senior Scientist Award: Cyrus Chothia". Bioinformatics. 31 (13): 2238–9. doi:10.1093/bioinformatics/btv218. PMID 26002905.
  72. ^ "Meet the ISCB Fellows Class of 2015". Archived from the original on 20 February 2015. Retrieved 15 February 2015.

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