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Coupling backbone flexibility and amino acid sequence selection in protein design.

A Su·S L Mayo
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Abstract

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 beta 1 domain (G beta 1). Concerted backbone motion was introduced by varying G beta 1'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 G beta 1's native supersecondary structure parameter values.

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AlgorithmsAmino Acid SequenceCircular DichroismMagnetic Resonance SpectroscopyMutagenesisProtein Structure, SecondaryProteinsThermodynamicsJournal ArticleResearch Support, Non-U.S. Gov't

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A Su, S L Mayo. 1997. Coupling backbone flexibility and amino acid sequence selection in protein design.. https://doi.org/10.1002/pro.5560060810

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