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 λ repressor characterized experimentally by Lim and Sauer1. 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.
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Lee, C., Levitt, M. Accurate prediction of the stability and activity effects of site-directed mutagenesis on a protein core. Nature 352, 448–451 (1991). https://doi.org/10.1038/352448a0
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DOI: https://doi.org/10.1038/352448a0
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