Hierarchical QSAR

Basak, S. C., Balasubramanian, K., Gute, B. D., Mills, D., Gorczynska, A., Roszak, S. Prediction of cellular toxicity of halocarbons from computed chemodescriptors A hierarchical QSAR approach. J. Chem. Inf. Comput. Sci. 2003, 43, 1103-1109. 

Gute, B. D., Grunwald, G. D., Basak, S. C. Prediction of the dermal penetration of polycyclic aromatic hydrocarbons (PAHs) A hierarchical QSAR approach. SAR QSAR Environ. Res. 1999, 10, 1-15. 

Basak, S. C., Natarajan, R., Mills, D. Structure-activity relationships for mosquito repellent aminoamides using the hierarchical QSAR method based on calculated molecular descriptors, 2005, pp. 958-963. 

Manga, N., Dully, J.C., Rowe, P.H., and Cronin, M.T.D. A hierarchical QSAR model for urinary excretion of drugs in humans as a predictive tool for... 

Gute, B.D. and Basak, S.C., Predicting acute toxicity (LC50) of benzene derivatives using theoretical molecular descriptors a hierarchical QSAR approach, SAP QSAR Environ. Res., 1, 117-131, 1997. 

Basak, S.C., Gute, B.D. and Grunwald, G.D. (1997c). Use of Topostructural, Topochemical, and Geometric Parameters in the Prediction of Vapor Pressure A Hierarchical QSAR Approach. J.Chem.Inf.Comput.ScL, 37, 651-655. 

Gute, B.D., Grunwald, G.D. and Basak, S.C. (1999). Prediction of the Dermal Penetration of Polycyclic Aromatic Hydrocarbons (PAHs) A Hierarchical QSAR Approach. SAR QSAR Environ.Res., 10,1-15. 

A Hierarchal QSAR Molecular Structure Calculator Applied to a Carcinogenic Nitrosamine Data Base... 

In general QSAR models can be constructed from any combination of the four levels of structure calculation. We are currently developing a software package to compute the different classes of molecular descriptors and to construct action models. This software package is being called "A Hierarchal QSAR Molecular Structure Calculator". 

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]. 

Balasubramanian, K. (2003b) Use of topological indices in predicting aryl hydrocarbon receptor binding potency of dibenzofurans a hierarchical QSAR approach. Indian J. Chem., 42, 1385—1391. 

Eriksson, L., Johansson, E., Lindgren, F., Sjostrom, M., Wold, S. Megavariate analysis of hierarchical QSAR data, J. Gomput.-Aided Mol. Des. 2002,16, 711-26. 

Topochemical, and Geometric Parameters in the Prediction of Vapor Pressure A Hierarchical QSAR Approach. 

Figure 4.10 Flow chart of hierarchic QSAR models for prediciting the biodegradability of alicyclic compounds (Degner, 1991 lUCT, 1992 OECD, 1993b). Reproduced with permission from OECD.

In previous studies, we have found our hierarchical QSAR approach to be successful in predicting properties, activities, and toxicities including ... 

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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