Topological QSAR analysis

A Brief Review of the QSAR Technique. Most of the 2D QSAR methods employ graph theoretic indices to characterize molecular structures, which have been extensively studied by Radic, Kier, and Hall [see 23]. Although these structural indices represent different aspects of the molecular structures, their physicochemical meaning is unclear. The successful applications of these topological indices combined with MLR analysis have been summarized recently. Similarly, the ADAPT system employs topological indices as well as other structural parameters (e.g., steric and quantum mechanical parameters) coupled with MLR method for QSAR analysis [24]. It has been extensively applied to QSAR/QSPR studies in analytical chemistry, toxicity analysis, and other biological activity prediction. On the other hand, parameters derived from various experiments through chemometric methods have also been used in the study of peptide QSAR, where partial least-squares (PLS) analysis has been employed [25]. 

Murcia-Soler M, Perez-Gimenez F, Naldo-Molina R, Salabert-Salvador MT, Garcla-March FJ, Cercos-del-Pozo RA et al. QSAR analysis of hypoglycaemic agents using the topological indices. J Chem Inf Comput Sci 2001 41 1345-54. 

Golbraikh, A., Bonchev, D., and Tropsha, A., Novel ZE-isomerism descriptors derived from molecular topology and their application to QSAR analysis, J. Chem. Inf. Comput. Sci., 42, 769-787, 2002. 

Computes topological indexes from molecular structures for use in QSAR analysis. PC and Macintosh. Also VAX version. 

Molecular Advanced Design systems for general molecular modeling. MAD TSAR for QSAR analysis, including computation of topological indices. IBM, Silicon Graphics, and Hewlett-Packard workstations. 

Mendiratta, S. and Madan, A.K. (1994). Structure-Activity Study on Antiviral 5-Vinylpyrimidine Nucleoside Analogs Using Wiener s Topological Index. J.Chem.Inf.Comput.ScL, 34,867-871. Menziani, M.C. and De Benedetti, P.G. (1992). Molecular Mechanics and Quantum Chemical QSAR Analysis in Carbonic Anhydrase Heterocyclic Sulfonamide Interactions. Struct. CherrL,... 

Rose, V. S., Croall, I. E, MacFie, H. J. H. An apphcation of unsupervised neural network methodology (Kohonen topology-preserving mapping) to QSAR analysis. Quant. Struct.-Act. Relat. 1991,10,6-15. 

Murda-Soler, M., Perez-Gimenez, F., Nalda-Molina, R., Salabert-Salvador, M.T., Garcfa-March, F.J., Cercos-del-Pozo, R.A. and Garrigues, T.M. (2001) QSAR analysis of hypoglycemic agents using the topological indices./. Chem. Inf. Comput. Sci., 41, 1345-1354. 

Investigation of chromatographic retention is one of the most active areas for QSAR studies using connectivity indexes and other topological indexes. Many papers have been written for this important area of analytical chemistry. Sabljic demonstrated that the connectivity indexes are very useful in the QSAR analysis of chromatographic retention and lists several references. In particular, he refers to analysis of chlorinated alkanes and benzenes. For 13 chlorinated benzenes he showed that the first-order index gives excellent correlation (r = 0.997 and 0.985) for retention on SE-30 and on Carbowax 20M, respectively. These regressions were better than ones based on the use of the Wiener number or the Balaban ] index, even with a heteroatom modification. The isomer pairs 1,3- and 1,4-dichlorobenzene as well as the other isomers are not discriminated by the first-order index alone. 

The statistics for this model are as follows = 0.83 and cross-validated r, = 0.79. Further QSAR analysis was carried out with E-state topological... 

Pyka, A. Study of lipophilicity and application of selected topological indexes in QSAR analysis of nicotinic acid... 

Many other topological indices can be defined, calculated by direct inspection of molecular graphs, and used in QSAR analysis. 

Properties may also be derived purely from two-dimensional descriptions of molecules. Many of these, such as connectivity indices, topological indices and substituent based parameters, can be calculated within Tsar. While these properties may not produce as accurate a description of molecules as do the three-dimensional properties, they may be more useful for some types of QSAR analysis, particularly for studies where molecular alignment is not possible. Also, as mentioned at the start, QSAR is a complex problem, where the initial data are not always clearly defined. In these cases, it can be the case that a cruder description of the molecules may give a better explanation of these less well defined data. 

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