Validation of a two-parameter quantitative structure-activity relationship as a legitimate tool for rational...

Previously reported rates of reaction between six mutant strains of the enzyme horseradish peroxidase (HRP) and a test substrate, 2-methoxyphenol, were found to correlate with characteristic binding distances computed using molecular simulation. The correlation (R(2) = 0.86) bears out a working hypothesis that, based on a quantitative structure-activity relationship (QSAR) we had previously developed for HRP, reductions in binding distances between the HRP enzyme and any selected substrate mediate increased enzyme reactivity towards that substrate. The results validate the use of QSAR as a quantitative means for formulating enzyme mutations designed to achieve enhanced HRP reactivity towards compounds of specific interest.