The local minima method (LMM) of pharmacophore determination: A protocol for predicting the bioactive conformation of small, conformationally flexible molecules

Journal of Chemical Information and Computer Sciences

Volumn 38, Issue 6, 1998, Pages 1125-1136

  Demeter, David A ^a   Weintraub, Herschel J R ^b   Knittel, James J ^c  

^a R W JOHNSON PHARMACEUTICAL RES I   (United States)

^b Helios Pharmaceuticals   (United States)

^c UNIVERSITY OF CINCINNATI   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DOPAMINE BETA MONOOXYGENASE; ENZYME INHIBITOR; IMIDAZOLE DERIVATIVE; LIGAND;

ALGORITHM; ARTICLE; BINDING SITE; CHEMICAL STRUCTURE; CHEMISTRY; CONFORMATION; DRUG ANTAGONISM; MOLECULAR WEIGHT;

ALGORITHMS; BINDING SITES; DOPAMINE BETA-HYDROXYLASE; ENZYME INHIBITORS; IMIDAZOLES; LIGANDS; MODELS, MOLECULAR; MOLECULAR CONFORMATION; MOLECULAR WEIGHT;

EID: 0032197017     PISSN: 00952338     EISSN: None     Source Type: Journal    
DOI: 10.1021/ci980404z     Document Type: Article

References (79)

1. Demeter, D. A. Development and Application of Potential Energy Surface Analysis and the Local Minima Method of Pharmacophore Determination. Ph.D. Dissertation, University of Cincinnati, 1994; pp 1-179.
2. (a) Villafranca, J. J.; Ash, D. E.; Colombo, G.; Fitzpatrick, P. F.; Papadopoulos, N. J.; Rajashekhar, B. Molecular Architecture of Proteins and Enzymes; Bradshaw, R. A., Tang, J., Eds.; Academic Press: Orlando, FL, 1985; pp 31-50.
3. (b) Stewart, L. C.; Klinman, J. P. Dopamine β-hydroxylase of adrenal chromaffin granules: structure and function. Annu. Rev. Biochem. 1988, 57, 551-592.
4. (c) Ash, D. E.; Papadopoulos, N. J.; Colombo, G.; Villafranca, J. J. Kinetic and spectroscopic studies of the interaction of copper with dopamine β-hydroxylase. J. Biol. Chem. 1984, 259, 3395-3398.
5. (d) Klinman, J. P.; Krueger, M.; Brenner, M.; Edmondson, D. E. Evidence for two copper atoms/subunit in dopamine β-monooxygenase catalysis. J. Biol. Chem. 1984, 259, 3399-3402.
6. Oka, M.; Kijikawa, K.; Ohuchi, T.; Yoshida, H.; Imaizumi, R. Distribution of dopamine-β-hydroxylase in subcellular fractions of adrenal medulla. Life Sci. 1967, 6, 461-465.
7. Stjarne, L.; Lishajko, F. Localization of different steps in noradrenaline synthesis to different fractions of a bovine splenic nerve homogenate. Biochem. Pharmacol. 1967, 16, 1719-1728.
8. Brenner, M. C.; Klinman, J. P. Correlation of Copper Valency with Product Formation in Single Turnovers of Dopamine β-Monooxygenase. Biochemistry 1989, 28, 4664-4670.
9. Klinman, J. P.; Dooley, D. M.; Duine, J. A.; Knowles, P. F.; Mondovi, B.; Villafranca, J. J. Status of the cofactor identity in copper oxidative enzymes. FEBS Lett. 1991, 282, 1-4.
10. DeWolf, W. E., Jr.; Chambers, P. A.; Southan, C.; Saunders, D.; Kruse, L. I. Inactivation of Dopamine β-Hydroxylase by β-Ethynyl-tyramine: Kinetic Characterization and Covalent Modification of an Active Site Peptide. Biochemistry 1989, 29, 3833-3842.
11. (a) Rosenberg, R. C.; Lovenberg, W. Dopamine-β-hydroxylase. Essays Neurochem. Neuropharm. 1980, 4, 163-209.
12. (b) Ljones, T.; Skotland, T. Copper Proteins and Copper Enzymes; Lontie, R., Ed.; CRC Press: Boca Raton, FL, 1984; Vol. 2, p 131.
13. (c) Villafranca, J. J. Copper Proteins; Spiro, T. G., Ed.; Wiley: New York, 1981; p 264.
14. (a) Axelrod, J. Dopamine-β-hydroxylase. Regulation of its synthesis and release from nerve terminals. Pharmacol. Rev. 1972, 24, 233-243.
15. (b) Sole, M. J.; Kamble, A. B.; Hussian, M. N. A Possible Change in the Rate Limiting Step for Cardiac Norepinephrine Synthesis in the Cardiomyopathic Syrian Hamster. Circ. Res. 1977, 41, 814-817.
16. (a) DeChamplain, J.; Farley, L.; Cousineau, D.; Ameringen, M. R. van, Circulating catechol amine levels in human and experimental hypertension. Circ. Res. 1976, 38, 109-114.
17. (b) DeQuattro, V.; Chan, S. Raised plasma-catecholamines in some patients with primary hypertension. Lancet 1972, 1, 806-809.
18. (c) Engelman, K.; Portnoy, B.; Sjoerdsma, A. Plasma catechol amine concentrations in patients with hypertension. Circ. Res., Suppl. 1970, 27, 141-146.
19. (d) Franco-Morselli, R.; Elghozi, J. L.; Joly, E.; Di Giuilio, S.; Meyer, P. Increased plasma adrenaline concentrations in benign essential hypertension. Br. Med. J. 1977, 2, 1251-1254.
20. (e) Goldstein, D. S. Plasma norepinephrine in essential hypertension. A study of the studies. Hypertension 1981, 3, 48-52.
21. (f) Louis, W. J.; Doyle, A. E.; Anavekar, S. Plasma norepinephrine levels in essential hyoertension. N. Engl. J. Med. 1973, 288, 599-601.
22. (g) Nagatsu, T.; Ikuta, K.; Numata (Sudo), Y.; Kato, T.; Sano, M.; Nagatsu, I.; Umezawa, H.; Matsuzaki, M.; Takeuchi, T. Vascular and brain dopamine β-hydroxylase activity in young spontaneously hypertensive rats. Science (Washington, D.C.) 1976, 191, 290-291.
23. (h) Fujita, K.; Teradaira, R.; Inoue, T.; Takahashi, H.; Beppu, H.; Kawai, K.; Maruta, K.; Yagyo, S.; Nagatsu, T. Stress-induced changes in in vivo and in vitro dopamine-β-hydroxylase activity in spontaneously hypertensive rats. Biochem. Med. 1982, 28, 340-346.
24. Chidsey, C. A.; Sonnenblick, E. H.; Morrow, A. G.; Braunwald, E. Norepinephrine stores and contractile force of papillary muscle from the failing human heart. Circulation 1966, 33, 43-51.
25. Ohlstein, E. H.; Kruse, L. I.; Ezekiel, M.; Sherman, S. S.; Erickson, R.; DeWolf, W. E., Jr.; Berkowitz, B. A. Cardiovascular effects of a new potent dopamine β-hydroxylase inhibitor in spontaneously hypertensive rats. J. Phamacol. Exp. Ther. 1987, 241, 554-559.
26. (a) Kruse, L. I.; Kaiser, C.; DeWolf, W. E., Jr.; Chambers, P. A.; Goodhart, P. J.; Ezekiel, M.; Ohlstein, E. H. β-Substituted Phenethyl-amines as High-Affinity Mechanism-Based Inhibitors of Dopamine β-Hydroxylase J. Med. Chem. 1988, 31, 704-706.
27. (b) Fitzpatrick, P. F.; Villafranca, J. J. Mechanism-based inhibitors of dopamine β-hydroxylase. Arch. Biochem. Biophys. 1987, 257, 231-250.
28. (c) May, S. W.; Wimalasena, K.; Herman, H. H.; Fowler, L. C.; Ciccarello, M. C.; Pollock, S. H. Novel antihypertensives targeted at dopamine β-monooxygenase: turnover-dependent cofactor depletion by phenyl aminoethyl selenide. J. Med. Chem. 1988, 31, 1066-1068.
29. Kruse, L. I.; DeWolf Jr., W. E.; Chambers, P. A.; Goodhart, P. J. Design and Kinetic Characterization of Multisubstrate Inhibitors of Dopamine β-Hydroxylase. Biochemistry 1986, 25, 7271-7278.
30. Kruse, L. I.; Kaiser, C.; DeWolf, W. E., Jr.; Frazee, J. S.; Garvey, E.; Hilbert, E. L.; Faulkner, W. A.; Flaim, K. E.; Sawyer, J. L.; Berkowitz, B. A. Multisubstrate inhibitors of Dopamine β-Hydroxylase. 1. Some 1-Phenyl and 1-Phenyl-Bridged Derivatives of Imidazole-2-thione. J. Med. Chem. 1986, 29, 2465-2472.
31. Kruse, L. I.; Kaiser, C.; DeWolf, W. E., Jr.; Frazee, J. S.; Ross, S. T.; Wawro, J.; Wise, M.; Flaim, K. E.; Sawyer, J. L.; Erickson, R. W.; Ezekiel, M.; Ohlstein, E. H.; Berkowitz, B. A. Multisubstrate Inhibitors of Dopamine β-Hydroxylase. 2. Structure-Activity relationships at the Phenethylamine Binding Site. J. Med. Chem. 1987, 30, 486-494.
32. Ross, S. T.; Kruse, L. I.; Ohlstein, E. H.; Erickson, R. W.; Ezekiel, M.; Flaim, K. E.; Sawyer, J. L.; Berkowitz, B. A. Inhibitors of Dopamine β-Hydroxylase. 3. Some 1-(Pyridylmethyl)imidazole-2-thiones. J. Med. Chem. 1987, 30, 1309-1313.
33. Kruse, L. I.; Kaiser, C.; DeWolf, W. E.; Finkelstein, J. A.; Frazee, J. S.; Hilbert, E. L.; Ross, S. T.; Flaim, K. E.; Sawyer, J. L. Some Benzyl-Substituted Imidazoles, Triazoles, Tetrazoles, Pyridinethiones, and Structural Relatives as Multisubstrate Inhibitors of Dopamine β-Hydroxylase. 4. Structure-Activity Relationships at the Copper Binding Site. J. Med. Chem. 1990, 33, 781-789.
34. Press: J. B. Pharmacologically Active Compounds and Other Thiophene Derivatives. In Thiophene and Its Derivatives; Gronowitz, S., Ed.; Wiley: New York, 1985; Vol. 44, Part 1, pp 353-456.
35. McCarthy, J. R.; Matthews, D. P.; Broersma, R. J.; McDermott, R. D.; Kastner, P. R.; Hornsperger, J.-M.; Demeter, D. A.; Weintraub, H. J. R.; Whitten, J. P. 1-(Thienylalkyl)imidazole-2(3H)-thiones as Potent Competitive Inhibitors of Dopamine β-Hydroxylase. J. Med. Chem. 1990, 33, 1866-1873.
36. Nakano, T.; Kobayashi, K.; Saito, S.; Fujita, K.; Nagatsu, T. Mouse dopamine β-hydroxylase: primary stucture deduced from the cDNA sequence and exon/intron organization of the gene. Biochem. Biophys. Res. Commun. 1992, 189, 590-599.
37. .McMahon, A.; Geertman, R.; Sabban, E. L. Rat dopamine β-hydroxylase: molecular cloning and characterization of the cDNA and regulation of the mRNA by resperine. J. Neurosci. Res. 1990, 25, 395-404.
38. (a) Wang, N.; Southan, C.; DeWolf, W. E., Jr.; Wells, T. N.; Kruse, L. I.; Leatherbarrow, R. J. Bovine dopamine β-hydroxylase, primary structure determined by cDNA cloning and amino acid sequencing. Biochemistry 1990, 29, 6466-6474.
39. (b) Wu, H. J.; Farmer, R. J.; Koop, A. H.; Rozansky, D. J.; O'Connor, D. T. Molecular cloning, structure, and expression of dopamine β-hydroxylase from bovine adrenal medulla. Journal of Neurochemistry 1990, 55, 97-105.
40. (c) Robertson, J. G.; Desai, P. R.; Kumar, A.; Farrington, G. K.; Fitzpatrick, P. F.; Villafranca, J. J. Primary amino acid sequence of bovine dopamine β-hydroxylase. J. Biol. Chem. 1990, 265, 1029-1035.
41. (d) Lewis, E. J.; Allison, S.; Fader, D.; Claflin, V.; Baizer, L. Bovine dopamine β-hydroxylase cDNA. Complete coding sequence and expression in mammalian cells with vaccinia virus vector. J. Biol. Chem. 1990, 265, 1021-1028.
42. (a) Kobayashi, K.; Kurosawa, Y.; Fujita, K.; Nagatsu, T. Human dopamine β-hydroxylase gene: two mRNA types having different 3′-terminal regions are produced through alternative polyadenylation. Nucleic Acids Research 1989, 17, 1089-1102.
43. (b) Lamouroux, A.; Vigny, A.; Faucon Biguet, N.; Darmon, M. C.; Franck, R.; Henry, J. P.; Mallet, J. The primary structure of human dopamine β-hydroxylase: insights into the relationship between the soluble and the membrane-bound forms of the enzyme. EMBO Journal 1987, 6, 3931-3937.
44. DeWolf, W. E., Jr.; Carr, S. A.; Varrichio, A.; Goodhart, P. J.; Mentzer, M. A.; Roberts, G. D.; Southan, C.; Dolle, R. E.; Kruse, L. I. Inactivation of Dopamine β-Hydroxylase by p-Cresol: Isolation and Characterization of Covalently Modified Active Site Peptides. Biochemistry 1988, 27, 9093-9101.
45. Southan, C.; DeWolf, W. E., Jr.; Kruse, L. I. Inactivation of dopamine β-hydroxylase by p-cresol: evidence for a second, minor site of covalent modification at tyrosine 357. Biochim. Biophys. Acta 1990, 1037, 256-258.
46. DeWolf, W. E., Jr.; Chambers, P. A.; Southan, C.; Saunders: D.; Kruse, L. I. Inactivation of Dopamine β-Hydroxylase by β-Ethynyl-tyramine: Kinetic Characterization and Covalent Modification of an Active Site Peptide. Biochemistry 1989, 28, 3833-3842.
47. Farrington, G. K.; Kumar, A.; Villafranca, J. J. Active Site Labeling of Dopamine β-Hydroxylase by Two Mechanism-based Inhibitors: 6-Hydroxybenzofuran and Phenylhydrazine. J. Biol. Chem. 1990, 265, 1036-1040.
48. Tainer, J. A.; Getzoff, E. D.; Beem, K. M.; Richardson, J. S.; Richardson, D. C. Determination and analysis of the 2 Å structure of copper, zinc superoxide dismutase. J. Mol. Biol. 1982, 160, 181-217.
49. Robertson, J. G.; Desai, P. R.; Kumar, A.; Farrington, G. K.; Fitzpatrick, P. F.; Villafranca, J. J. Primary amino acid sequence of bovine dopamine β-hydroxylase. J. Biol. Chem. 1990, 265, 1029-1035.
50. Pettingill, T. M.; Strange, R. W.; Blackburn, N. J. Carbonmonoxy Dopamine β-Hydroxylase: Structural Characterization by Fourier Transform Infrared, Fluorescence, and X-ray Absorption Spectroscopy. J. Biol. Chem. 1991, 266, 16996-17003.
51. Blackburn, N. J.; Hasnain, S. S.; Pettingill, T. M.; Strange, R. W. Copper K-Extended X-ray Absorption Fine Structure Studies of Oxidized and Reduced Dopamine β-Hydroxylase. J. Biol. Chem. 1991, 266, 23120-23127.
52. Scott, R. A.; Sullivan, R. J.; DeWolf, W. E., Jr.; Dolle, R. E.; Kruse, L. I. The Copper Sites of Dopamine β-Hydroxylase: An X-ray Absorption Spectroscopic Study. Biochemistry 1988, 27, 5411-5417.
53. Blumberg, W. E.; Desai, P. R.; Powers, L.; Freedman, J. H.; Villafranca, J. J. X-ray Absorption Spectroscopic Study of the Active Copper Sites in Dopamine β-Hydroxylase. J. Biol. Chem. 1989, 264, 6029-6032.
54. McCracken, J.; Desai, P. R.; Papadopoulos, N. J.; Villafranca, J. J.; Peisach, J. Electron spin-echo studies of the copper(II) binding sites in dopamine β-hydroxylase. Biochemistry 1988, 27, 4133-4137.
55. Blackburn, N. J.; Pettingill, T. M.; Seagraves, K. S.; Shigeta, R. T. Characterization of a carbon monxide complex of reduced dopamine β-hydroxylase. Evidence for inequivalence of the Cu(I) centers. J. Biol. Chem. 1990, 265, 15383-15386.
56. Farger, L. Y.; Alben, J. O. Structure of the carbon monoxide binding site of hemocyanins studied by Fourier transform infrared spectroscopy. Biochemistry 1972, 11, 4786-4792.
57. (a) Volbeda, A.; Hol, W. G. J. Crystal structure of hexameric haemocyanin from Panulirus interruptus refined at 3.2 Å resolution. J. Mol. Biol. 1989, 209, 249-279.
58. (b) Solomon, E. I. In Metal Ions in Biology; Spiro, T. G., Ed.; John Wiley & Sons: New York, 1981; pp 40-108.
59. (a) Marshall, G. R.; Barry, C. D.; Bosshard, H. E.; Dammkoehler, R. A.; Dunn, D. A. The conformational parameter in drug design: the active analogue approach. In Computer Assisted Drug Design: Olson, E. C., Christofferson, R. E., Eds.; American Chemical Society: ACS Symposium Series, Washington, D.C., 1979; Vol. 112, pp 205-226.
60. (b) Mayer, D.; Naylor, C. B.; Motoc, I.; Marshall, G. R. A unique geometry of the active site of angiotensin-converting enzyme consistent with structure-activity studies. J. Comput.-Aided Mol. Design 1987, 1, 3-16.
61. (a) Cramer III, R. D.; Patterson, D. E.; Bunce, J. D. Comparative molecular-field analysis (COMFA). 1. Effect of shape on binding of steroids to carrier proteins. J. Am. Chem. Soc. 1988, 110, 5959-5967.
62. (b) Marshall, G. R.; Cramer III, R. D. 3-Dimensional structure activity relationships. Trends in Pharmacol. Sci. 1988, 9, 285-289.
63. (c) Allen, M. S.; Yan, Y. C.; Trudell, M. L.; Narayanan, K.; Schindler, L. R.; Martin, M. J.; Schultz, C.; Hagen, T. J.; Koehler, K. F.; Codding, P. W.; Skolnick, P.; Cook, J. M. Synthetic and computer-assisted analyses of the pharmacophore for the benzodiazepine receptor inverse agonist site. J. Med. Chem. 1990, 33, 2343-2357.
64. Dunn, W. J.; Wold, S.; Edlund, U.; Hellberg, S. Multivariate Structure-Activity Relationships Between Data from a Battery of Biological Tests and an Ensemble of Structure Descriptors: The PLS Methodol. Quant. Struct.-Act. Relat. 1984, 3, 131-137.
65. Kim, K. H. Use of Indicator Variable in Comparative Molecular Field Analysis. Med. Chem. Res. 1993, 3, 257-267.
66. Tripos Associates, 1699 S. Hanley Road, Suite 303, St. Louis, MO 63144.
67. (a) Clark, M.; Cramer III, R. D.; Van Opdenbosch, N. Validation of the General Purpose Tripos 5.2 Force Field. J. Comput. Chem. 1989, 10(8), 982-1012.
68. (b) Sybyl 6.0 Theory Manual, Appendix 2.2, pp 2421-2423, October 1992.
69. Dewar, M. J. S.; Thiel, W. Ground-states of molecules. 38. MNDO Method - approximations and parameters. J. Am. Chem. Soc. 1977, 99, 4899-4907.
70. Stewart, J. J. P. MOPAC 5.0, QCPE program no. 455.
71. Clark, D. E.; Willett, P.; Kenny, P. W. Pharmacophoric pattern matching in files of three-dimensional chemical structures: Use of bounded distance matrixes for the representation and searching of conformationally flexible molecules. J. Mol. Graphics 1992, 10(4), 194-204.
72. Martin, Y. C.; Bures, M. G.; Danaher, E. A.; DeLazzer, J.; Lico, I.; Pavlik, P. A. A fast approach to pharmacophore mapping and its application to dopaminergic and benzodiazepine agonists. J. Comput.-Aided. Mol Design. 1993, 7, 83-102.
73. Golender, V.; Vesterman, B.; Vorpagel, E. APEX-3D Expert System for Drug Design. Network Sci. 1996, 2, http://www.awod.com/netsci/ Issues/Jan96/feature3.html (no pp given).
74. (a) Sprague, P. W.; Hoffmann, R. CATALYST pharmacophore models and their utility as queries for searching 3D databases. Comput.-Assisted Lead Find. Optim. [Eur. Symp. Quant. Struct.-Act. Relat.], 11th; Eds.; Van de Waterbeemd, H.; Testa, B.; Folkers, G. Verlag Helvetica Chimica Acta: Basel, Switzerland; 1997; pp 225-240.
75. (a) Sprague, P. W.; Hoffmann, R. CATALYST pharmacophore models and their utility as queries for searching 3D databases. Comput.-Assisted Lead Find. Optim. [Eur. Symp. Quant. Struct.-Act. Relat.], 11th; Eds.; Van de Waterbeemd, H.; Testa, B.; Folkers, G. Verlag Helvetica Chimica Acta: Basel, Switzerland; 1997; pp 225-240.
76. (b) Kahn, S. D.; Hahn, M.; Parish, D. The use of feature-and shape-based database searching techniques to identify new drug templates. Book of Abstracts, 211th ACS National Meeting, New Orleans, LA; American Chemical Society, Washington, D.C. March 24-28 1996, CINF-048.
77. (c) Kaminski, J. J.; Rane, D. F.; Snow, M. E.; Weber, L.; Rothofsky, M. L.; Anderson, S. D.; Lin, S. L. Identification of Novel Farnesyl Protein Transferase Inhibitors Using Three-Dimensional Database Searching Methods. J. Med. Chem. 1997, 40(25), 4103-4112.
78. Pearlman, R. S. Receptor-Relevant Chemistry Subspaces and Other Recent Advances. Presented at the Tripos Users Group Meeting; Somerset, NJ, May 19, 1998.
79. Nicklaus, M. C.; Wang, S.; Driscoll, J. S.; Milne, G. W. A. Conformational Changes of Small Molecules Binding to Proteins. Bioorg., Med. Chem. 1995, 3(4), 411-428.