Multiconformational composite molecular potential fields in the analysis of drug action. I. Methodology and first evaluation using 5-HT and histamine action as examples
10.1007/bf00125171
Crossref journal-article
Springer Science and Business Media LLC
Journal of Computer-Aided Molecular Design (297)
Bibliography

Vinter, J. G., & Trollope, K. I. (1995). Multiconformational composite molecular potential fields in the analysis of drug action. I. Methodology and first evaluation using 5-HT and histamine action as examples. Journal of Computer-Aided Molecular Design, 9(4), 297–307.

Authors 2
  1. J. G. Vinter (first)
  2. K. I. Trollope (additional)
References 28 Referenced 15
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  14. In accordance with the Reaction Isotherm, less than 0.1% of the higher energy conformer will exist at body temperature when it lies 2.7 kcal/mol above the lowest energy conformer.
  15. The primary sorting factor, to select the best 50 overlays, uses the Coulombic overlay energy only. Although this is regarded as an ?energy?, its quantitative value has no physical significance because such interactions would not occur in nature. Fields of this kind reorganise themselves as the two species closely approach and finally dock. However, recent work (not reported here) has suggested that Coulombic overlay energies may reflect a qualitative binding strength order. Secondary factors, used to order the 50 overlays in different ways, need to (i) take account of the excess or relief of energy necessary for the receptor to incorporate a given conformation; and (ii) consider that an overlay between drug conformers and a specific common conformer may occur more than once and be included in some ?entropic? adjustment. Furthermore, Boltzmann statistics need to be applied across the comparisons. These issues are being addressed.
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  27. We have completed a fuller study, to be published in due course, accounting for tautomeric variability. This has suggested a subtle interplay of 1N- and 3N-tautomeric interchanges in histamine which seems to correlate with agonism and antagonism (see Nederkoorn, P.H.J., Vernooijs, P., Donné-Op den Kelder, G.M., Baerends, E.J. and Timmerman, H., J. Mol. Graphics, 12 (1994) 242). There is no justification in reproducing the individual conformers of histamine in Fig. 9, as they are only variations on the 1N-tautomer. However, it is worth noting that, even at the elementary level of analysis presented here, the conformers associated with a particular colour code were members of distinct conformational families, in a similar way to those found for 5-HT. (10.1016/0263-7855(94)80101-0) / J. Mol. Graphics by P.H.J. Nederkoorn (1994)
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Dates
Type When
Created 20 years, 9 months ago (Oct. 31, 2004, 1:54 a.m.)
Deposited 6 years, 4 months ago (April 3, 2019, 1:18 a.m.)
Indexed 2 months, 3 weeks ago (June 6, 2025, 5:08 a.m.)
Issued 30 years ago (Aug. 1, 1995)
Published 30 years ago (Aug. 1, 1995)
Published Print 30 years ago (Aug. 1, 1995)
Funders 0

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@article{Vinter_1995, title={Multiconformational composite molecular potential fields in the analysis of drug action. I. Methodology and first evaluation using 5-HT and histamine action as examples}, volume={9}, ISSN={1573-4951}, url={http://dx.doi.org/10.1007/bf00125171}, DOI={10.1007/bf00125171}, number={4}, journal={Journal of Computer-Aided Molecular Design}, publisher={Springer Science and Business Media LLC}, author={Vinter, J. G. and Trollope, K. I.}, year={1995}, month=aug, pages={297–307} }