Abstract
We used a novel charge optimization technique to study the small ribonuclease barnase and to analyze its interaction with a natural tight binding inhibitor, the protein barstar. The approach uses a continuum model to explicitly determine the charge distributions that lead to the most favorable electrostatic contribution to binding when competing desolvation and interaction effects are included. Given its backbone fold, barstar is electrostatically optimized for tight binding to barnase when compared with mutants where residues have been substituted with one of the 20 common amino acids. Natural proteins thus appear to use optimization of electrostatic interactions as one strategy for achieving tight binding.
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Acknowledgements
We thank B. Honig for making the delphi and grasp computer programs available, M. Karplus for charmm, R.J. Vanderbei for loqo, and members of our research group, particularly J.A. Caravella and M.A. Ohliger, for helpful discussions and critical reading of an earlier draft of the manuscript. This work was supported by the National Institutes of Health.
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Lee, LP., Tidor, B. Barstar is electrostatically optimized for tight binding to barnase. Nat Struct Mol Biol 8, 73–76 (2001). https://doi.org/10.1038/83082
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DOI: https://doi.org/10.1038/83082
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