title: Prediction of enzyme kinetic parameters based on statistical learning.
abstract: Values of enzyme kinetic parameters are a key requisite for the kinetic modelling of biochemical systems. For most kinetic parameters, however, not even an order of magnitude is known, so the estimation of model parameters from experimental data remains a major task in systems biology. We propose a statistical approach to infer values for kinetic parameters across species and enzymes making use of parameter values that have been measured under various conditions and that are nowadays stored in databases. We fit the data by a statistical regression model in which the substrate, the combination enzyme-substrate and the combination organism-substrate have a linear effect on the logarithmic parameter value. As a result, we obtain predictions and error ranges for unknown enzyme parameters. We apply our method to decadic logarithmic Michaelis-Menten constants from the BRENDA database and confirm the results with leave-one-out crossvalidation, in which we mask one value at a time and predict it from the remaining data. For a set of 8 metabolites we obtain a standard prediction error of 1.01 for the deviation of the predicted values from the true values, while the standard deviation of the experimental values is 1.16. The method is applicable to other types of kinetic parameters for which many experimental data are available.
authors.affiliation: Max Planck Institute for Molecular Genetics, Ihnestrasse 63-73, 14195 Berlin, Germany. borger@molgen.mpg.de
authors.forename: Simon
authors.initials: S
authors.lastname: Borger
authors.forename: Wolfram
authors.initials: W
authors.lastname: Liebermeister
authors.forename: Edda
authors.initials: E
authors.lastname: Klipp
mesh_terms: D030562:Databases, Protein; D004798:Enzymes / Q000737:chemistry* / Q000378:metabolism* / Q000502:physiology; D007700:Kinetics; D007858:Learning; D008954:Models, Biological; D015233:Models, Statistical; D011237:Predictive Value of Tests; D012044:Regression Analysis; D013379:Substrate Specificity
chemical_list: D004798:Enzymes