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    Nature. 1991 Aug 1;352(6334):448-51.

    Accurate prediction of the stability and activity effects of site-directed mutagenesis on a protein core.

    Source

    Beckman Laboratories for Structural Biology, Department of Cell Biology, Stanford University Medical Center, California 94305.

    Abstract

    Theoretical prediction of the structure, stability and activity of proteins, an important unsolved problem in molecular biology, would be of use for guiding site-directed mutagenesis and other protein-engineering techniques. X-ray diffraction studies have provided extensive structural information for many proteins, challenging theorists to develop reliable techniques able to use such knowledge as a base for prediction of mutants' characteristics. Here we report theoretical calculation of stabilization energies for 78 triple-site sequence variants of lambda repressor characterized experimentally by Lim and Sauer. The calculated energies correlate with the mutants' measured activities; active and inactive mutations are discriminated with 92% reliability. They correlate even more directly with the mutants' thermostabilities, correctly identifying two of the mutants to be more stable than the wild type.

    PMID:
    1861725
    [PubMed - indexed for MEDLINE]

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