Three-dimensional quantitative structure-activity relationships from molecular similarity matrices and genetic neural networks. 1. Method and validations

Journal of Medicinal Chemistry
S S So, M Karplus

Abstract

The utility of genetic neural network (GNN) to obtain quantitative structure-activity relationships (QSAR) from molecular similarity matrices is described. In this application, the corticosteroid-binding globulin (CBG) binding affinity of the well-known steroid data set is examined. Excellent predictivity can be obtained through the use of either electrostatic or shape properties alone. Statistical validation using a standard randomization test indicates that the results are not due to chance correlations. Application of GNN on the combined electrostatic and shape matrix produces a six-descriptor model with a cross-validated r2 value of 0.94. The model is superior to those obtained from partial least-squares and genetic regressions, and it also compares favorably with the results for the same data set from other established 3D QSAR methods. The theoretical basis for the use of molecular similarity in QSAR is discussed.

References

Oct 1, 1979·Journal of Medicinal Chemistry·J G Topliss, R P Edwards
Oct 1, 1991·Journal of Computer-aided Molecular Design·A Y Meyer, W G Richards
Jan 1, 1983·Molecular and Cellular Biochemistry·U Westphal
Oct 28, 1994·Journal of Medicinal Chemistry·D T ManallackD J Livingstone
May 24, 1996·Journal of Medicinal Chemistry·B D Silverman, D E Platt
Feb 1, 1996·Journal of Computer-aided Molecular Design·C A MontanariJ C Mitchell
Jun 1, 1996·Journal of Computer-aided Molecular Design·T I Oprea, A E García
Aug 1, 1988·Journal of the American Chemical Society·R D CramerJ D Bunce

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Citations

May 8, 1999·Medicinal Research Reviews·I KövesdiP Mátyus
Oct 19, 2005·Journal of Computer-aided Molecular Design·Yovani Marrero-Ponce, Juan A Castillo-Garit
Apr 12, 2006·Journal of Computer-aided Molecular Design·Zeljko DebeljakMarica Medić-Sarić
Oct 24, 2002·Biochemical Pharmacology·Nicole A KratochwilPaul R Gerber
Nov 27, 1998·Progress in Biophysics and Molecular Biology·G Schneider, P Wrede
May 18, 2000·Journal of Pharmaceutical and Biomedical Analysis·S Agatonovic-Kustrin, R Beresford
Aug 6, 1998·Current Opinion in Chemical Biology·L Weber
Oct 19, 2011·SAR and QSAR in Environmental Research·J SridharC L Klein Stevens
Aug 22, 2012·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Gregory SliwoskiJens Meiler
Oct 7, 2014·Wiley Interdisciplinary Reviews. Computational Molecular Science·John B O Mitchell
Nov 18, 2006·Journal of Molecular Graphics & Modelling·Juan A Castillo-GaritRichard Rotondo
Feb 3, 2011·Journal of Enzyme Inhibition and Medicinal Chemistry·Shreekant DeshpandeYenamandra S Prabhakar
Mar 19, 2015·SAR and QSAR in Environmental Research·P AshrafiY Sun
Feb 7, 2016·Chemical Biology & Drug Design·Xinli DuanMing Lei
Jul 9, 2008·Journal of Enzyme Inhibition and Medicinal Chemistry·Shreekant DeshpandeYenamandra S Prabhakar
May 13, 2008·Journal of Computational Chemistry·Juan A Castillo-GaritVicente Romero-Zaldivar
Oct 14, 2010·Journal of Enzyme Inhibition and Medicinal Chemistry·Brij K SharmaYenamandra S Prabhakar
Sep 28, 2012·Journal of Computational Chemistry·Stephen J BarigyeOscar Martínez-Santiago
May 11, 2019·Current Topics in Medicinal Chemistry·Oscar Martínez-SantiagoHai Pham-The
Jun 25, 2009·Journal of Enzyme Inhibition and Medicinal Chemistry·Susheela SharmaY S Prabhakar
Aug 19, 2009·Journal of Physics. Condensed Matter : an Institute of Physics Journal·Fernando A EscobedoJuan C Araque
Feb 26, 2005·Journal of Computer-aided Molecular Design·Knut Baumann, Nikolaus Stiefl
Mar 10, 2010·European Journal of Medicinal Chemistry·Brij Kishore SharmaPradeep Pilania
Mar 30, 2010·European Journal of Medicinal Chemistry·Veerasamy RavichandranArumugam Dhanaraj Sokkalingam

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