| Computational Design of Thermostabilizing D-Amino Acid Substitutions. | |
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MedLine Citation:
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PMID: 21978298 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Judicious incorporation of D-amino acids in engineered proteins confer many advantages such as preventing degradation by endogenous proteases, and designing novel structures and functions not accessible to homochiral polypeptides. Glycine to D-alanine substitutions at the carboxy-termini can stabilize α-helices by reducing conformational entropy. Beyond alanine, we propose additional side chain effects on the degree of stabilization conferred by D-amino acid substitutions. A detailed, molecular understanding of backbone and side chain interactions is important for developing rational, broadly applicable strategies in using D-amino acids to increase protein thermostability. Insight from structural bioinformatics combined with computational protein design can successfully guide the selection of stabilizing D-amino acid mutations. Substituting a key glycine in the Trp-Cage mini-protein with D-Gln dramatically stabilizes the fold without altering the protein backbone. Stabilities of individual substitutions can be understood in terms of the balance of intramolecular forces at both the α-helix C-terminus and throughout the protein. |
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Authors:
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Agustina Rodriguez-Granillo; Srinivas V Annavarapu; Lei Zhang; Ronald L Koder; Vikas Nanda |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-10-6 |
Journal Detail:
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Title: Journal of the American Chemical Society Volume: - ISSN: 1520-5126 ISO Abbreviation: - Publication Date: 2011 Oct |
Date Detail:
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Created Date: 2011-10-7 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7503056 Medline TA: J Am Chem Soc Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
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