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Geoffrey Chang is a professor at the University of California, San Diego's Skaggs School of Pharmacy and Pharmaceutical Sciences and Department of Pharmacology, School of Medicine. His laboratory focuses on the structural biology of integral membrane proteins, particularly exploring X-ray crystallography techniques for solving the tertiary structures of membrane proteins that are notoriously resistant to crystallization. The laboratory has specialized in structures of multidrug resistance transporter proteins in bacteria. In 2001, while a faculty member of The Scripps Research Institute, Chang was awarded a Beckman Young Investigators Award, designed to support researchers early in their academic careers, for his work on the structural biology of multidrug resistance.〔The Scripps Research Institute News and Views. (In Brief ) 1(9): 2 Apr 2001. Access date 17 Jan 2001.〕 Chang announced a move from Scripps to neighboring UC San Diego in 2012. In 2007, Chang and coauthors retracted five previously published papers describing the structures of three multidrug transporter proteins after another research group published a widely differing structure, which led to the discovery of a critical bug in the Chang group's custom software tools.〔Miller G. (2006). Scientific publishing. A scientist's nightmare: software problem leads to five retractions. ''Science'' 314(5807):1856-7. PMID 17185570〕 Since that time, however, Chang has published other papers in the field of structural biology,〔Aller S. et al. (2009). Structure of P-Glycoprotein Reveals a Molecular Basis for Poly-Specific Drug Binding. ''Science'' 323 (5922): 1718 - 1722. http://www.sciencemag.org/cgi/content/abstract/323/5922/1718〕〔He et al., "Structure of a Cation‐bound Multidrug and Toxic Compound Extrusion Transporter," http://www.nature.com/nature/journal/vaop/ncurrent/abs/nature09408.html〕 and has been awarded a EUREKA grant, "for exceptionally innovative research projects that could have an extraordinarily significant impact on many areas of science," from the National Institutes of Health.〔Scripps Research Institute Geoffrey Chang Wins EUREKA Award http://www.scripps.edu/newsandviews/e_20100920/etc.html〕 ==Retracted papers== Chang and coauthors published papers on the structures of multidrug resistance transporters known as EmrE, and MsbA. Although the initial structures were widely considered puzzling in the field due to their unexpected placement of their ATP binding sites in the assembled dimer,〔Higgins CF, Linton KJ. (2001). Structural biology. The xyz of ABC transporters. ''Science'' 293(5536):1782-4. PMID 11546861 〕 the publication of an additional structure in the same protein family indicated that the Chang structures were unlikely to represent the biologically active conformation of the molecules.〔Dawson RJ, Locher KP. (2006). Structure of a bacterial multidrug ABC transporter. ''Nature'' 443(7108):180-5. PMID 16943773 〕 Chang and coauthors issued retractions of their structural papers on EmrE, and MsbA, citing an error in an internal software utility as the source of the data misinterpretation that led to the appearance of wrongly assembled dimers.〔Chang G, Roth CB, Reyes CL, Pornillos O, Chen YJ, Chen AP. (2006). Retraction. ''Science'' 314(5807):1875 PMID 17185584 〕〔 The application of a popular protein structure validation tool to one of the retracted MsbA structures results in scores that indicate severe errors in this structure.〔Wiederstein M, Sippl MJ. (2007). ProSA-web: interactive web service for the recognition of errors in three-dimensional structures of proteins. ''Nucleic Acids Res'', . PMID 17517781 〕 The following papers were retracted in 2007:〔〔Gawrylewski A. (2006). Retractions unsettle structural bio: Recent findings upend conclusions from five highly-cited papers ''The Scientist'' 4 Jan 2007 (Free full text ) Access date 17 Jan 2007.〕 * Chang G, Roth CB. (2001) Structure of MsbA from E. coli: a homolog of the multidrug resistance ATP binding cassette (ABC) transporters. ''Science'' 293(5536):1793-800. PMID 11546864 * Pornillos O, Chen YJ, Chen AP, Chang G. (2005) X-ray structure of the EmrE multidrug transporter in complex with a substrate. ''Science'' 310(5756):1950-3. PMID 16373573 * Reyes CL, Chang G. (2005) Structure of the ABC transporter MsbA in complex with ADP.vanadate and lipopolysaccharide. ''Science'' 308(5724):1028-31. PMID 15890884 * Chang G. (2003). Structure of MsbA from Vibrio cholera: a multidrug resistance ABC transporter homolog in a closed conformation. ''J Mol Biol'' 330(2):419-30. PMID 12823979 * Ma C, Chang G. (2004). Structure of the multidrug resistance efflux transporter EmrE from Escherichia coli. ''Proc Natl Acad Sci USA'' 101(9):2852-7. PMID 14970332 The episode has been referenced in both the scientific and popular media as a case study motivating improved software engineering practices in computational biology. 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「Geoffrey Chang」の詳細全文を読む スポンサード リンク
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