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Protein Engineering vol. 3 no. 8 pp. 673-675, 1990
© 1990 Oxford University Press

RESEARCH-ARTICLE

The interpretation of site-directed mutagenesis experiments by linear free energy relations

John E. Straub and Martin Karplus

Department of Chemistry, Harvard University Cambridge, MA 02138, USA

Fersht and co-workers have applied a linear free energy relation (Brønsted equation) to analyze site-directed mutagenesis experiments involving the enzyme tyrosyl-tRNA synthetase and have suggested that the Brønsted exponent is linearly correlated with the value of the reaction coordinate at the transition state. We point out that when the mutants differ solely through the formation or deletion of a hydrogen bond away from the reaction center, a linear free energy relation is expected only in limiting cases for which the Brønsted relation exponent is 0, 1 or {infty}. The results may be correlated with a conformational coordinate but not with the development of the reaction coordinate per se.

Keywords: Brønsted plots/site-directed mutagenesis/linear free energy relations

Received November 7, 1989;
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