Hierarchical QSAR applications

With a different meaning, the term hierarchical QSAR was also used to denote the application of Partial Least Squares (PLS) and Principal Component Analysis (PGA) to different logical blocks of molecular descriptors to summarize descriptors of each block into a few latent variables or components, which were called supervariables [Eriksson, Johansson et al, 2002]. 

For the three classes of molecules for which detailed HiQSARs have been discussed here, viz., dibenzofurans, heteroaromatic and aromatic amines, and imidazole Cox-2 inhibitors, a hierarchical QSAR approach using a combination of topostructural, topochemical, 3D, and quantum chemical descriptors produced high quality models. Such models, based on purely calculated descriptors, can find application in the routine drug design process as shown in Fig. 11. 

Kuz min VE, Muratov EN, Artemenko AG et al (2009) Consensus QSAR modeling of phosphor-containing chiral AChE inhibitors. QSAR Comb Sci 28(6-7) 664-677 Kuz min VE, Artemenko AG, Muratov EN et al (2010) Virtual screening and molecular design based on hierarchic QSAR technology. In Puzyn T, Leszczynski J, Cronin MTD (eds) Recent advances in QSAR studies methods and applications. Challenges and advances in computational chemistry and physics, vol 8. Springer Science+Business Media BV, Dordrecht, pp 127-176... 

Carhart RE, Smith DH, Venkataraghavan R (1985) Atom pairs as molecular features in structure-activity studies. Definition and application. J Chem Inf Comput Sci 25 64-73 Kuz min VE, Artemenko AG, Muratov EN (2008) Hierarchical QSAR technology on the base of Simplex representation of molecular structure. J Comput Aided Mol Des 22 403 21 Lindenberg M, Kopp S, Dressman JB (2004) Classification of orally administered drugs on the World Health Organization Model list of essential medicines according to the biopharmaceutics classification system. Eur J Pharm Biopharm 58 265-278... 

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