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Replacing affinity with binding kinetics in QSAR studies resolves otherwise confounded effects
Author(s) -
Andersson Karl,
Hämäläinen Markku D.
Publication year - 2006
Publication title -
journal of chemometrics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.47
H-Index - 92
eISSN - 1099-128X
pISSN - 0886-9383
DOI - 10.1002/cem.1010
Subject(s) - quantitative structure–activity relationship , dissociation rate , chemistry , kinetics , dissociation (chemistry) , interpretation (philosophy) , stereochemistry , biological system , econometrics , computational chemistry , computer science , mathematics , biology , physics , quantum mechanics , programming language
Steady‐state binding affinity is a commonly used response variable in quantitative structure‐activity relationship (QSAR) studies. In this paper we show that affinity alone may introduce unnecessary noise to the model or even cause model failure. Binding affinity is a ratio between the dissociation rate and association rate. Mathematical modeling of a ratio with unknown variation structure of nominator and denominator is difficult and the interpretation of the resulting model might be meaningless under certain circumstances. Commercially available biosensors can be used for measurement of binding kinetics enabling separate modeling of association and dissociation rates. In this paper we discuss the problems caused by the confounded effect in the compiled response affinity and show examples where separate modeling of the rate constants improves the interpretation of QSAR models. Copyright © 2007 John Wiley & Sons, Ltd.