An Evaluation of Some SVM Heuristics for Predicting Activity on pKi Assays

An agonist is a signalling molecule which binds to a receptor inducing a confor mational change which produces a response An antagonist is a drug which attenuates the e ect of an agonist Antagonists may be competitive non competitive or uncompetitive A competitive antagonist binds to a region of the receptor which overlaps the region bound by an agonist The agonist and antagonist compete for the same binding site and cannot simultaneously occupy the receptor The potency of a competitive antagonist is quanti ed by the equi librium dissociation constant KB as determined in a functional assay This is the concentration of antagonist which would occupy of the receptors at equilibrium This may be determined by Schild analysis a concentration response curve is plotted for the agonist in the presence of varying quantities of the antagonist Theoretically this value should be the same as the KI value determined in a radioligand competition binding assay In this assay the ago nist is radio labelled and is screened at only one concentration usually below its equilibrium dissociation constant for the receptor KD The speci c level of binding of the agonist is then determined in the presence of a range of concentra tions of a competing non radioactive compound The data for each competing ligand are usually tted to a hyperbolic equation from which the IC can be determined The IC is the concentration of antagonist required to reduce the speci c binding of the radioligand by This is then converted to a KI value by the Cheng Pruso equation