Evaluation of extended parameter sets for the 3D-QSAR technique MaP: Implications for interpretability and model quality exemplified by antimalarially active naphthylisoquinoline alkaloids

Journal of Computer-Aided Molecular Design - Tập 17 - Trang 347-365 - 2003
Nikolaus Stiefl1, Gerhard Bringmann2, Christian Rummey2, Knut Baumann1
1Department of Pharmacy and Food Chemistry, University of Würzburg, Am Hubland, Würzburg, Germany
2Institute of Organic Chemistry, University of Würzburg, Am Hubland, Würzburg, Germany

Tóm tắt

The 3D-QSAR technique MaP (Mapping Property distributions of molecular surfaces) characterises biologically active compounds in terms of the distribution of their surface properties (H-bond donor, H-bond acceptor, hydrophilic, weakly hydrophobic, strongly hydrophobic). The MaP descriptor is alignment-independent and yields chemically intuitive models. In this study, the impact of different operational parameters on the interpretability and model quality was investigated. Based on a set of antimalarially active naphtylisoquinoline alkaloids the effect of hydrophobicity assignment as well as the differentiation of H-bond propensity was evaluated according to a full factorial design. It turns out, that including different categories for H-bond donor strength significantly improved interpretability, reduced model complexity, and made possible the derivation of a novel pharmacophore hypothesis for this dataset. Further analysis of the factorial design reveals, that MaP models are robust to parameter changes and generate consistent models for different parameter settings.

Tài liệu tham khảo

Cramer, R.D., Patterson, D.E., Bunce, J.D., J. Am. Chem. Soc., 110 (1988) 5959.

Klebe, G., Abraham, U., Mietzner, T., J. Med. Chem., 37 (1994) 4130.

Kim, K.H., Martin, Y.C., J. Org. Chem., 56 (1991) 2723.

Pastor M, Cruciani, G., Watson, K.A., J. Med. Chem., 40 (1997) 4089.

Pastor, M., Cruciani, G., McLay, I., Pickett, S., Clementi, S., J. Med. Chem., 43 (2000) 3233.

Stiefl, N., Baumann, K., J. Med. Chem., 46 (2003) 1390.

Goodford, P.J., J. Med. Chem., 28 (1985) 849.

Fontaine, F., Pastor, M., Sanz, F., In M. Ford, D. Livingstone (Eds.), Proceedings of the 14th European Symposium on QSAR, Blackwell Science, Oxford, UK. In Press.

Bringmann, G., Rummey C., J. Chem. Inf. Comput. Sci., 43 (2003) 304.

Bringmann, G., Pokorny, F., In Cordell, G.A. (Ed.), The Alkaloids. Vol. 46, Academic Press, New York, 1995, pp. 127–271.

Bringmann, G., Feineis, D., Act. Chim. Thérapeut., 26 (2000) 151.

Bringmann, G., In Vial, H., Fairlamb, A., Ridley, R. (Eds.), Guidelines and Issue for the Discovery and Drug Development Against Tropical Diseases, World Health Organisation, Geneva, 2002, in print.

Bravi, G., Gancia, E., Green, D.V.S., Hann, M.M., Methods and Principles in Medicinal Chemistry, 10 (Virtual Screening for Bioactive Molecules) (2000) 81.

François, G., Chimanuka, B., Timperman, G., Holenz, J., Plaizier-Vercammen, J., Aké Assi, L., Bringmann, G., Parasitol. Res., 85 (1999) 935.

Chimanuka, B., François, G., Timperman, G., Heyden, Y.V., Holenz, J., Plaizier-Vercammen, J., Bringmann, G., Parasitol. Res., 87 (2001) 795.

François, G., Timperman, G., Steenackers, T., Aké Assi, L., Holenz, J., Bringmann, G., Parasitol. Res., 83 (1997) 673.

François, G., Timperman, G., Eling, W., Aké Assi, L., Holenz, J., Bringmann, G., Antimicrob. Agents Chemother., 41 (1997) 2533.

Carhart, R.E., Smith, D.H., Venkataraghavan, R., J. Chem. Inf. Comput. Sci., 25 (1985) 64.

Connolly, M.L., J. Appl. Cryst., 16 (1983) 548.

Sanner, M.F., Spehner, J.-C., Olson, A.J., Biopolymers, 38 (1996) 305.

Pascual-Ahuir, J.L., Silla, E., J. Comp. Chem., 11 (1990) 1047.

Rocchia, W., Sridharan, S., Nicholls, A., Alexov, E., Chiabrera, A., Honig, B., J. Comp. Chem., 23 (2002) 128.

Todeschini, R., Consonni, V., Handbook of Molecular Descriptors, Wiley-VCH, Weinheim, 2000.

Arnold, H., In Hahn, T. (Ed.), International Tables for Crystallography. Volume A: Space-Group Symmetry, D. Reidel Publishing Company, Dordrecht 1983, pp. 70–75.

SYBYL® 6.8 Tripos Inc., 1699 South Hanley Rd., St. Louis, Missouri, 63144, USA, 2000.

Ghose, A.K., Viswanadhan, V.N., Wendoloski, J.J., J. Phys. Chem. A, 102 (1998) 3762.

Hahn, M., J. Med. Chem., 38, 2080.

Heiden, W., Moeckel, G., Brickmann, J., J. Comput.-Aided Mol. Des., 7 (1993), 503.

Sheridan, R.P., Miller, M.D., Underwood D.J., Kearsley, S.K., J. Chem. Inf. Comput. Sci., 36, (1996) 128.

Brown, R.D., Martin, Y.C., J. Chem. Inf. Comput. Sci., 36 (1996) 572.

Martens H., Naes T., Multivariate Calibration, John Wiley bibitem Sons, Chichester, UK, 1989.

Baumann, K., Albert, H., von Korff, M., J. Chemom., 16 (2002) 339.

Draper, N.R., Smith, H., Applied Regression Analysis, John Wiley & Sons, New York, USA, 1981.

Baumann, K. Habilitation-Thesis. Universität Würzburg, Germany, 2003.

Geisser S., J. Amer. Statist. Assoc., 70 (1975) 320.

Baumann, K., von Korff, M., Albert, H., J. Chemom., 16 (2002) 351.

Baumann, K., Quant. Struct.-Act. Relat., 21 (2002) 507.

Burman, P.A., Biometrika, 76 (1989) 503.

Topliss, J.G., Edwards, R.P., J. Med. Chem., 22 (1979) 1238.

Klopman, G., Kalos, A.N., J. Comput. Chem., 6 (1985) 492.

Faber, N.M., Chemom. Intell. Lab. Sys., 49 (1999) 79.

Wu, W., Walczak, B., Massart, D.L., Heuerding, S., Erni, F., Last, I.R., Prebble, K.A., Chemom. Intell. Lab. Sys., 33 (1996) 35.

Kennard, R.W., Stone, L.A., Technometrics, 11 (1969) 137.

de Groot, P.J., Postma, G.J., Melssen, W.J., Buydens, L.M.C., Anal. Chim. Acta 392 (1999) 67–75.

Jouan-Rimbaud, D., Bouveresse, E., Massart, D.L., de Noord, O.E., Anal. Chim. Acta 388 (1999) 283–301.

De Maesschalk, R., Jouan-Rimbaud, D., Massart, D.L., Chemom. Intell. Lab. Sys., 50 (2000) 1.

Ghafourian, T., Dearden, J.C., J. Pharm. Pharmacol., 52 (2000) 603.

Abraham, M.H., Chem. Soc. Rev., 22 (1993) 73.

Raevsky, O.A., J. Phys. Org. Chem., 10 (1997) 405.

Bringmann, G., Messer, K., Wohlfarth, M., Kraus, J., Dumbuya, K., Rückert, M., Anal. Chem., 71 (1999) 2678.

Zucchini W., J. Math. Psychol., 44 (2000) 41.

Unger, S.H., Hansch, C., J. Med. Chem., 16 (1973) 745.

Golbraikh, A., Tropsha, A., J. Mol. Graphics Modell. 20 (2002) 269–276.

Manly B.F.J., Randomization, Bootstrap and Monte Carlo Methods in Biology (2nd Ed.), Chapman&Hall/CRC, Boca Raton, 2001.

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Thông tin xuất bản

Journal of Computer-Aided Molecular Design

Tập 17

347-365

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