Quantitative structure activity relationship methods

Ekins S, De Groot MJ, Jones JP. Pharmacophore and three-dimensional quantitative structure activity relationship methods for modeling cytochrome P450 active sites. Drug Metab Dispos 2001 29 936-44. 

Meylan, W.M. Howard, P.H. (2003) A Review of Quantitative Structure-Activity Relationship Methods for the Prediction of Atmospheric Qxidation of Qrganic Chemicals. Environmental Toxicology and Chemistry, 22(8), 1724—1732. 

R. Perkins, H. Pang, W. Tong, W. J. Welsh (2003). Quantitative structure-activity relationship methods perspectives on drug discovery and toxicology. Environ. Toxicol. Chem. 22 1666-1679. 

Tong, W., Lowis, D.R., Perkins, R., Chen, Y., Welsh, W.J., Goddette, D.W., Heritage, T.W., and Sheehan, D.M., Evaluation of quantitative structure-activity relationship methods for large-scale prediction of chemicals binding to the estrogen receptor, J. Chem. Inf. Comput. Sci., 38, 669-677, 1998. 

Contrasted with Three Other Quantitative Structure—Activity Relationships Methods. 

Kamenska, V., Mekenyan, O., Sterev, A. and Nedjalkova, Z. (1996). Application of the Dynamic Quantitative Structure-Activity Relationship Method for Modeling Antibacterial Activity of Quinolone Derivatives. Arzneim.Forsch., 46,423-428. 

Nirmalakhandan, N.N. and Speece, R.E. (1993). Prediction of Activated Carbon Adsorption Capacities for Organic Vapors Using Quantitative Structure-Activity Relationship Methods. Environ.Sci. Technoi, 27,1512-1516. 

Because of fhe stereospecifity of biological effects, QSAR (quantitative structure-activity relationships) methods must be capable of taking into account atomic chiralities. Indeed, one of fhe most popular 3D-QSAR methods, CoMFA and other CoMFA-like methods take into account chirality by default, since fhe molecular fields of chiral isomers are different If compounds are highly flexible and no experimental structural information about fhe receptor-ligand complexes is available, CoMFA (and CoMFA-like) methods are not always applicable. Several shortcomings and problems have motivated researchers to consider improvements to these techniques. The first idea for improvement was to modify the conventional 2D descriptors to make them chirahty-sensitive [1]. 

Nedjalkova, Z. (1996) Application of the dynamic quantitative structure-activity relationship method for modeling antibacterial activity of quinolone derivatives. Arzneim. Forsch. (German), 46, 423 28. 

Woolfrey, J.R., Avery, M.A. and Doweyko, A.M. (1998) Comparison of 3D quantitative structure-activity relationship methods analysis of the in vitro antimalarial activity of 154 artemisinin analogues by hypothetical active-site lattice and comparative molecular field analysis./. Comput. Aid. Mol. Des., 12, 165-181. 

Ghose AK, Crippen GM. Modeling the benzodiazepine receptor binding site by the general three-dimensional structure-directed quantitative structure-activity relationship method REMOTEDISC. Mol Pharmacol 1990 37 725-734. 

In spite of such interesting examples, it still remains an open question how molecular similarity is defined with respect to immunological response, since it is also known that cross-reactivity exists in some instances between STLs and mono- as well as diterpenoids [74], It appears therefore a promising topic for future studies to investigate this issue in more detail (i.e. with large sets of compounds and applying quantitative structure-activity relationship methods) in order to elucidate the general rules by which specificity in ACD cross-sensitivity is determined. 

Rodgers AD, Zhu H, Fourches D, Rusyn I, Tropsha A (2010) Modeling liver-related adverse effects of drugs using nearest neighbor quantitative structure-activity relationship method. 

A. K. Ghose and G. M. Crippen, Mol. Pharmacol., 37, 725 (1990). Modeling the Benzodiazepine Receptor Binding Site by the General Three-Dimensional Structure-Directed Quantitative Structure-Activity Relationship Method REMOTEDISC. 

Modeling and applications of enzyme kinetics and quantitative structure activity relationship methods is a vast field and its importance in the years to come in bioinfo and chemoinformatics sciences and biotechnology is only going to increase. The author welcomes and thanks the readers in advance for any constructive observations, corrections and suggestions, which can be incorporated and updated in its fiuther editions. 

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