3D QSAR applications

Norinder, U. Single and domain made variable selection in 3D QSAR applications./. Chemometrics 1996, 10, 95-105. 

The popularity of commercial programs such as Comparative Molecular Field Analysis (4,12) (CoMFA) and Catalyst (13) has limited both the evaluation and use of other QSAR methodologies. Often well-known issues associated with CoMFA and Catalyst have come to be viewed as shortcomings that simply are accepted as working limitations in a 3D-QSAR analysis. In this section we challenge this position and present 3D- and nD-QSAR methods that are able to overcome some of the issues associated with current mainstream 3D-QSAR application products. 

Norinder, U. Single and Domain Made Variable Selection in 3D QSAR Applications./. Chemom. 1996, 10, 95—105. 

However, the initial hype is over and the number of new 3D QSAR applications has been more or less constant in the last years. One major drawback of 3D QSAR is that it is not applicable to huge datasets containing more than several hundreds of compounds as is possible with high-throughput... 

Nilsson J, Multiway Calibration in 3D QSAR. Applications to dopamine receptor ligands, Ph.D. thesis, University of Groningen, 1998. 

Greenidge PA, Weiser J. A comparison of methods for pharmacophore generation with the catalyst software and their use for 3D-QSAR application to a set of 4-aminopyridine thrombin inhibitors. Min Rev Med Chem 2001 1 79-87. 

Two groups have developed hydrophobic fields for CoMFA 3D-QSAR applications. The HINT (hydrophobic interaction) program calculates the hydrophobic field of a molecule using Hansch-Leo hydrophobic constants scaled by surface area and a distance-dependent function. The MLP program... 

U. Norinder, /. Chemometrics, 10, 95 (1996). Single and Domain Mode-Viriable Selection in 3D QSAR Applications. 

Kubinyi H (Editor) 1993. 3D QSAR in Drug Design, Theory, Methods and Applications. Leiden, ESCOM. 

Once a number of lead compounds have been found, computational and laboratory techniques are very successful in rehning the molecular structures to yield greater drug activity and fewer side elfects. This is done both in the laboratory and computationally by examining the molecular structures to determine which aspects are responsible for both the drug activity and the side effects. These are the QSAR techniques described in Chapter 30. Recently, 3D QSAR has become very popular for this type of application. These techniques have been very successful in the rehnement of lead compounds. 

Gaillard, P., Carrupt, P. A., Testa, B Boudon, A. Molecular lipophilicity potential, a tool in 3D QSAR Method and applications, f Comput.-Aided Mol. Des. 1994, 8, 83-96. 

Gussio, R., Pattabieaman, N., Kellogg, G.E., Zahaeevitz, D.W. Use of 3D QSAR methodology for data mining the National Cancer Institute Repository of Small Molecules application to HlV-1 reverse transcriptase inhibition. Methods 1998, 14, 255-263. 

The methodology of 3D-QSAR can be robust for constructing QSAR models utilizing the structure of the compounds and how they will interact with the receptor however, there are several open questions that can complicate any application of this paradigm. The first and most prominent question is Which conformation of the molecule should be used This problem is considered... 

Kubinyi, H., Ed. (1993) 3D QSAR in drug design theory methods and applications, Escom Science, Leiden, pp.523-550. 

Pearlman, R.S. (1993) 3D molecular structures generation and use in 3D searching, in 3D QSAR in Drug Design. Theory Methods and Applications, 1st edn (ed. H. Kubinyi), FSCOM Science Publishers, Leiden, pp. 41—79. 

Marshall, G.R., Binding-site modeling of unknown receptors. In 3D QSAR in Drug Design, Theory Methods and Applications, Kubinyi, H. (ed.). ESCOM, Leiden, 1993, pp. 80-116. 

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