Molecular modeling metabolism

A. M. ter laak, N. P. E. Vermeulen, Molecular-modeling approaches to predict metabolism and toxicity, in Pharmacokinetic Optimization in Drug Research, B. Testa, H. van de Water-beemd, G. Folkers, R. Guy (Eds.), Wiley-VCH, Weinheim, 2001,... 

Isobutylene, polymerization of, 1207 Isocyanate. Hofmann rearrangement and,933-934 Isoelectric point (pJ), 1024 calculation of, 1024 table of, 1018-1019 lsoleucine, metabolism of, 911 molecular model of, 304 structure and properties of, 1018 Isomer, conformational, 93 Isomerase, 1041-1042 Isomers, 81... 

Wiseman H, Lewis DFV. The metabolism of tamoxifen by human cytochromes P450 is rationalized by molecular modelling of the enzyme substrate interac-... 

Lewis DF, Eddershaw PJ, Goldfarb PS, Tarbit MH. 1997. Molecular modelling of cytochrome P4502D6 CYP2D6) based on an alignment with CYP102 structural studies on specific CYP2D6 substrate metabolism. Xenobiotica 27 319-339. 

Consider a molecular structure, which is the most important unifying information model in chemistry. Molecular structures appear in knowledgebases that represent catalogs of commercially available chemicals, pharmacology of named drugs, natural sources of bioactive molecules, protein-ligand interactions, measured molecular bioactivities, metabolic pathways, abstracted research literature, databases of synthetic reactions, and so on. 

As a possible alternative to in vitro metabolism studies, QSAR and molecular modelling may play an increasing role. Quantitative stracture-pharmacokinetic relationships (QSPR) have been studied for nearly three decades [42,45-52]. These are often based on classical QSAR approaches based on multiple linear regression. In its most simple form, the relationship between PK properties and lipophilicity has been discussed by various workers in the field [36, 49, 50]. 

Lewis, D. F. and Lake, B. G. (2002) Species differences in coumarin metabolism a molecular modelling evaluation of CYP2A interactions. Xenobiotica 32, 547-561. 

Buettner, R., Parhofer, K. G., Woenckhaus, M., Wrede, . E., Kunz-Schughart, L. A., Scholmerich, J., and Bollheimer, L. C. (2006). Defining high-fat-diet rat models Metabolic and molecular effects of different fat types. J. Mol. Endocrinol. 36, 485-501. 

Lewis, D.F.V., Bird, M.G. Parke, D.V. (1997) Molecular modelling of CYP2E1 enzymes Irom rat, mouse and man an explanation for species differences in butadiene metabolism and potential carcinogenicity, and rationalization of CYP2E substrate specificity. Toxicology, 118, 93-113... 

An intensely interested audience awaits the crystallographer s final molecular model. This audience includes researchers studying the same molecule by other methods, such as spectroscopy or kinetics, or studying metabolic pathways or diseases in which the molecule is involved. The model may serve as a basis for understanding the properties of the protein and its behavior in bio-... 

Comparative molecular Leld analysis (CoMFA) is another promising approach developed in recent years for QSAR study. CoMFA is a molecular modeling technique forthe determination of molecular stericand electrostatic force Lelds (Tripos, 1992). It has been successfully used in deriving molecular descriptors for prediction of the bioactivity of steroids (Cramer etal., 1988), molecular Lux through a polymer membrane (Liu and Matheson, 1994), and metabolism and cytochrome p450 enzyme activities (Long and V felker, 2003). 

Lewis DF, Gillam EMJ, Everett SA, et al. Molecular modelling of human CYP1B1 substrate interactions and investigation of allelic variant effects on metabolism. Chem Biol Interact 2003 145 281-295. 

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