Active conformation quantitative structure-activity

GR Marshall, CD Barry, HE Bosshard, RA Dammkoehler, DA Dunn. The conformational parameter m drug design The active analog approach. ACS Symp Ser 112 205-226, 1979. JL Fauchere, ed. QSAR Quantitative Structure-Activity Relationships m Drug Design. New York Alan R Liss, 1989, pp 177-181. 

Certain computational methodologies such as some approaches to quantitative structure-activity relationship (QSAR) studies use 3D ligand structures [37, 38]. These methods generally assume that a bioactive conformation has been estab-Hshed for a set of molecules and that these conformers can be ahgned in a maimer that reflects the relative orientation they would adopt in a binding site. It is thus... 

Rastelli, G., Fanelli, F., Menziani, M.C., Cocchi, M. and De Benedetti, P.G. (1991) Conformational analysis, molecular modeling and quantitative structure-activity relationships studies of 2,4-diamino-6,7-dimethoxy-2-substituted quinazoline al-adrenergic antagonists. Journal of Molecular Structure (Theochem), 251, 307—318. 

KARMA is an interactive computer assisted drug design tool that incorporates quantitative structure-activity relationships (QSAR), conformational analysis, and three-dimensional graphics. It represents a novel approach to receptor mapping analysis when the x-ray structure of the receptor site is not known, karma utilizes real time interactive three-dimensional color computer graphics combined with numerical computations and symbolic manipulation techniques from the field of artificial intelligence. 

Computational chemistry methodology is finding increasing application to the design of new flavoring agents. This chapter surveys several useful techniques linear free energy relationships, quantitative structure-activity relationships, conformational analysis, electronic structure calculations, and statistical methods. Applications to the study of artificial sweeteners are described. 

Sotomatsu, T., Nakagawa, N., Fujita, T. (1987) Quantitative structure-activity studies of benzoylphenylurea larvicides. IV. Benzoyl ortho substituent effects and molecular conformation. Pestic. Biochem. Physiol. 27, 156-164. 

Bradbury, S.P., Mekenyan, O.G., and Ankley, G.T, Quantitative structure-activity relationships for polychlorinated hydroxybiphenyl estrogen receptor binding affinity an assessment of conformer flexibility, Environ. Toxicol. Chem., 15, 1945-1954, 1996. 

In an attempt to learn more about the nature of the plastoquinone binding site, we have analyzed the displacement behaviour of 25 different 1,4-benzoquinones to DCMU. A quantitative structure activity relationship revealed that the displacing activity of a quinone toward DCMU is governed by the redox potential and the geometrical conformation of the quinone (30). 

Waller, C.L., Wyrick, S.D., Kemp, W.E., Park, H.M. and Smith, FT. (1994). Conformational Analysis, Molecular Modeling, and Quantitative Structure-Activity Relationship Studies of Agents for the Inhibition of Astrocytic Chloride Transport. Pharm.Res., JJ, 47-53. 

Zhang et al. [36] combine DFT-based conformation analysis with quantitative structure-activity relationship (QSAR) analysis. They looked at bioactive conformations for 25 cyclic imide derivatives as proto-porphyrinogen oxidase (PPO) inhibitors. PPO is the last common enzyme in the biosynthetic... 

Under these circumstances, it is inevitable to estimate the active conformation of a chemical by another approach. The quantitative structure-activity relationship (QSAR) O) is one of the important approaches, particularly when the target site of a biologically active compound is unknown. Although X-ray crystallography is also helpful to estimate the active conformation, it provides the conformational information in a solid phase. More important is the conformation of a chemical in solution, which can be assigned in part by spectroscopic studies. Nuclear magnetic resonance (NMR) spectroscopy has been utilized to estimate the relative orientation of each atom in a molecule (2-5). Infra-red ( IR) spectroscopy is sometimes a useful tool, especially when hydrogen bonds are present ( ). Recently,... 

Caron, G., Ermondi, G. Influence of conformation on GRIND-based three-dimensional quantitative structure-activity relationship (3D-QSAR). J. Med. Chem. 2007. ASAP Article 10.1021/jm0704651... 

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