Prediction of binding affinities

RH Smith Jr, WL Jorgensen, J Tirado-Rives, ML Lamb, PAJ Janssen, CJ Michejda, MBK Smith. Prediction of binding affinities for TIBO inhibitors of HIV-1 reverse transcriptase using Monte Carlo simulations m a linear response method. J Med Chem 41 5272-5286, 1998. 

Bravi G, Wikel JH. Application of MS-WHIM descriptors 1. Introduction of new molecular surface properties and 2. Prediction of binding affinity data. 

T. I. Oprea and G. R. Marshall, Receptor based prediction of binding affinities, Perspect. 

Oprea, T.l. and Marshall, G.R. Receptor-based prediction of binding affinities. In 3D-QSAR in Drug Design, Kubinyi, H., Folkers, G., and Martin, Y.C. (Eds.). Kluwer/ESCOM, Dordrecht, NL, 1998, 35-61. 

Head, R.D., Smythe, M.L, Oprea, T.I., Waller, C.L., Greene, S.M., and Marsllall, G.R. VALIDATE A new method for the receptor-based prediction of binding affinities of novel ligands. 

Receptor-based Prediction of Binding Affinities of Novel Ugands./. Am. Chem. Soc. 1996, 778, 3959-3969. 

Chem. Soc., 118, 3959 (1996). VALIDATE A New Method for the Receptor-Based Prediction of Binding Affinities of Novel Ligands. 

Apart from the disadvantages listed above, the following two problems commonly arise (1) protein flexibility is not taken into sufficient consideration, and (2) the prediction of binding affinities between the proteins and ligands is not particularly accurate. Since both methods have advantages and disadvantages, the selection of the strategy depends on objectives of the lead identification and the situation. 

Finally, a consensus analysis using the two approaches (Raptor and Quasar) was achieved as, on average, the calculated activities of the training set differ by a factor 2.2 in K, and those of the test set by a factor 2.8 when predicted by Quasar and Raptor, respectively. It is important to note this size of deviation corresponds to the uncertainties in the underlying biological assays. Employing two different concepts for the prediction of binding affinities... 

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