Coupling backbone flexibility and amino acid sequence selection in protein design

Using a protein design algorithm that considers side‐chain packing quantitatively, the effect of explicit backbone motion on the selection of amino acids in protein design was assessed in the core of the streptococcal protein G β1 domain (Gβ1). Concerted backbone motion was introduced by varying Gβ1...

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Bibliographic Details
Published in:Protein science 1997-08, Vol.6 (8), p.1701-1707
Main Authors: Su, Alyce, Mayo, Stephen L.
Format: Article
Language:English
Subjects:
Algorithms
Amino Acid Sequence
backbone degrees of freedom
Circular Dichroism
Magnetic Resonance Spectroscopy
Mutagenesis
protein design
protein G
Protein Structure, Secondary
Proteins - chemistry
supersecondary structure parameters
Thermodynamics
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Summary:Using a protein design algorithm that considers side‐chain packing quantitatively, the effect of explicit backbone motion on the selection of amino acids in protein design was assessed in the core of the streptococcal protein G β1 domain (Gβ1). Concerted backbone motion was introduced by varying Gβ1′s supersecondary structure parameter values. The stability and structural flexibility of seven of the redesigned proteins were determined experimentally and showed that core variants containing as many as 6 of 10 possible mutations retain native‐like properties. This result demonstrates that backbone flexibility can be combined explicitly with amino acid side‐chain selection and that the selection algorithm is sufficiently robust to tolerate perturbations as large as 15% of Gβ1's native supersecondary structure parameter values.
ISSN:0961-8368
1469-896X
DOI:10.1002/pro.5560060810