Molecular modeling and QSAR

Kaur, J. Zhang, M. Q. Molecular modelling and QSAR of reversible acetylcholinesterase inhibitors. Curr. Med. Chem., 2000, 7(3) 273-294. 

Uhrig U, Holtje HD, Mannhold R, Weber H, Lemoine H. Molecular modeling and QSAR studies on K(ATP) channel openers of the benzopyran type. J Mol Graph Model 2002 21 37-45. 

Hemmateenejad, B., Miri, R., Tabarzad, M., Jafarpour, M. and Zand, F. (2004) Molecular modeling and QSAR analysis of the anticonvulsant activity of some N-phenyl-N°-(4-pyridinyl)-urea derivatives./. Mol. Struct. (Theochem), 684, 43-49. 

Recently, Keimowitz et al [38], aware that the cannabinoid side chain is a key pharmacophore, studied a series of 36 side-chain substituted A8-THCs with a wide range of pharmacological potency using computational molecular modelling and QSAR analysis. They showed that for optimum affinity and potency, the side chain must have conformational freedom that allows its terminus to fold back and come into proximity with the phenolic ring. In vivo THC is oxidized to the more potent ll-OH-A9-THC. Modifications of this structure yield 9-nor-9P-OH-hexahydrocannobinol (HHC) that has exhibited enhanced analgesic activity. 

Computational Tools and Biological Applications, F. Sanz,. Giraldo, and F. Manaut, Eds., J. R. Prous, Barcelona, 1995, pp. 451-456. The Basis of Crossreactivity for a Series of Steroids Binding to a Monoclonal Antibody Against Progesterone (DB3). A Molecular Modeling and QSAR Study. 

Lopez de Brinas, E., et al. (2000) European symposium on QSAR molecular modeling and prediction of bioactivity, Copenhagen, Denmark. 

Lee, J., Richburg, J.H., Younkin, S.C. Boekelheide, K. (1997) The Fas system is a key regulator of germ cell apoptosis in the testes. Endocrinology, 128, 2081-2088 Lewis, D.F.V Lake, B.G. (1993) Interaction of some peroxisome prolrferators with the mouse liver peroxisome proliferator-activated receptor (PPAR) a molecular modelling and quantitative stracture-activity relationship (QSAR) study. Xenobiotica, 23, 79-96 Lewis, L.M., Flechtner, T.W., Kerkay, J., Pearson, K.H. Nakamoto, S. (1978) Bis(2-ethyl-hexyl) phthalate concentrations in the serum of hemodialysis patients. Clin. Chem., 24, 741-746... 

Many software packages have been developed for calculation of molecular descriptors. Table 5.5 shows some software employed for molecular modeling, quantum-chemical calculations, molecular dynamics, and QSARs. 

Sippl, W., Contreras, J.M., Rival, Y.M., Wermuth, C. G. Comparative Molecular Field Analysis of Aminopyridazine Acetylcholinesterase Inhibitors. In Proceedings of the 12th European Symposium on QSAR - Molecular Modelling and Predicting of Bioactivity, Gundertofte, K. (ed.), Plenum Press, Copenhagen, 1998. 

Cruciani G, Crivori P, Carrupt PA, Testa B (2000) Molecular fields in quantitative structure-permeation relationships The VolSurf approach. Theochem 503 17-30 Cruciani G, Pastor M, Clementi S (2000) Handling information from 3D GRID maps for QSAR studies. In Gun-dertofte K, Jorgensen FS (eds) Molecular modelling and prediction of bioactivity, proceedings of the 12th European symposium on quantitative structure-activity relationships (QSAR 98). Plenum Press, New York, pp 73-81 Cruciani G, Pastor M, Guba W (2000) VolSurf A new tool for the pharmacokinetic optimization of lead compounds. Eur J Pharm Sd 11 S29-S39... 

Hopfinger, A.J., Compadre, R.L.L., Koehler, M.G., Emery, S. and Seydel, J.K. (1987). An Extended QSAR Analysis of Some 4-Aminodiphenylsulfone Antibacterial Agents Using Molecular Modeling and LFE-Relationships. Quant. Struct.-ActRelat, 6,111-117. 

Contents I. Introduction 34 II. Molecular Descriptors and Physicochemical Properties 36 III. Molecular Databases and Chemical Space 37 IV. Chemoinformatics in Food Chemistry 40 V. Examples of Molecular Similarity, Pharmacophore Modeling, Molecular Docking, and QSAR in Food or Food-Related Components 43 A. Molecular similarity 43 B. Pharmacophore model 47 C. QSAR and QSPR 48 D. Molecular docking 49 VI. Concluding Remarks and Perspectives 52 Acknowledgments 53 References 53... 

PHARMACOPHORE MODELING, MOLECULAR DOCKING, AND QSAR IN FOOD OR FOOD-RELATED COMPONENTS... 

Going deeper into the comparison and classification of chemical structures, a set of computational techniques are available. This section is organized to present a brief description of currently used methodologies, namely molecular similarity, pharmacophore modeling, molecular docking, and QSAR followed by application of these methods to food-related components. 

McFarland, J.W., Raevsky, O.A. and Wilkerson, W.W. (1999) Hydrogen bond acceptor and donor factors, Ca and Q new QSAR descriptors, in Molecular Modeling and Prediction of Bioactivity (eds K. Gundertofte and K. Jorgensen), Kluwer Academic/Plenum Publishers, USA, pp. 280-281. 

Bersuker, LB., Bahgeci, S., Boggs, J.E. and Pearlman, R.S. (1999a) A novel electron-conformational approach to molecular modeling for QSAR by identification of pharmacophore and antipharmacophore shielding. SAP QSAR Environ. Res., 10, 157-173. 

At step 2 of the Data Analysis Wizard (MetaDrug ) (Fig. 4) select the similarity cutoff to be applied to generate the list of structurally-similar database compounds and the molecular properties and QSAR models to be calculated. Default activity values for defining matches to individual QSAR models can be changed here also. 

Lemmen, C. Lengauer. T. In Molecular Modelling and Prediction of Bioactivity, Proceedings of the 12th European Symposium on Quantitative Structure-Activity Relationships (QSAR 98) Gunder-lofte, K. Jorgensen, F.S. (Eds.), Plenum Press, New York 1999, in press. 

Wold, S., Sjostrom, M., Andersson, P.M., Linusson, A., Edman, M., Lundstedt, T., Norden, B., Sandberg, M., and Uppg rd, L. Multivariate Design and Modelling in QSAR, Combinatorial Chemistry, and Bioinformatics. In Molecular Modeling and Prediction of Bioactivity. Plenum Press, in press, 1999. 

Cruciani, G., Pastor, M. and Clementi, S. (1999) Handling information from 3D grid maps for QSAR studies. In Gundertofte, K. and Jorgensen, F.S. (eds). Molecular Modeling and Prediction of Bioactivity. Kluwer, New York. 

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