Computational Design of a Single Amino Acid Sequence that Can Switch between Two Distinct Protein Folds.
The functions of many proteins are mediated by specific conformational changes, and therefore the ability to design primary sequences capable of secondary and tertiary changes is an important step toward the creation of novel functional proteins. To this end, we have developed an algorithm that can...
| Publicado en: | Journal of the American Chemical Society Vol. 128; no. 4; pp. 1154 - 1162 |
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| Autores principales: | , |
| Formato: | Artículo |
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American Chemical Society
2/1/2006
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=hlh&AN=20241741&site=ehost-live header: @attributes: shortDbName: hlh uiTerm: 20241741 longDbName: Humanities International Complete uiTag: AN controlInfo: bkinfo: jinfo: jid: 00027863 ACS jtl: Journal of the American Chemical Society issn: 00027863 maglogo: N pubinfo: dt: 2/1/2006 vid: 128 iid: 4 pid: 997 pub: American Chemical Society artinfo: ui: 20241741 10.1021/ja054718w ppf: 1154 ppct: 8 formats: tig: atl: Computational Design of a Single Amino Acid Sequence that Can Switch between Two Distinct Protein Folds. aug: au: Ambroggio, Xavier I. Kuhlman, Brian affil: Department of Biochemistry and Biophysics, University of North Carolina, Campus Box 7260, Chapel Hill, North Carolina 27599. su: Protein analysis Amino acids Protein folding Biomolecules Monte Carlo method Computer software development sug: subj: Protein analysis Amino acids Protein folding Biomolecules Monte Carlo method Computer software development ab: The functions of many proteins are mediated by specific conformational changes, and therefore the ability to design primary sequences capable of secondary and tertiary changes is an important step toward the creation of novel functional proteins. To this end, we have developed an algorithm that can optimize a single amino acid sequence for multiple target structures. The algorithm consists of an outer loop, in which sequence space is sampled by a Monte Carlo search with simulated annealing, and an inner loop, in which the effect of a given mutation is evaluated on the various target structures by using the rotamer packing routine and composite energy function of the protein design software, RosettaDesign. We have experimentally tested the method by designing a peptide, Sw2, which can be switched from a 2Cys-2His zinc finger-like fold to a trimeric coiled-coil fold, depending upon the pH or the presence of transition metals. Physical characterization of Sw2 confirms that it is able to reversibly adopt each intended target fold. pubtype: Academic Journal doctype: Article src: R language: English refInfo: copyright: @attributes: flag: Y dt: @attributes: year: 2006 holdings: @attributes: islocal: N |
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