Enzyme binding selectivity prediction: α-thrombin vs trypsin inhibition

Journal of Chemical Information and Computer Sciences

Volumn 44, Issue 5, 2004, Pages 1872-1882

  Mlinsek, G ^a   Novic, M ^a   Kotnik, M ^b   Solmajer, T ^a,b  

^a National Institute of Chemistry   (Venezuela)

^b Lek dd   (Slovenia)

Author keywords

[No Author keywords available]

Indexed keywords

BINDING CONSTANTS; ENZYME BINDING; INHIBITORS; MOLECULAR COMPLEX;

COMPLEXATION; DATABASE SYSTEMS; DRUG PRODUCTS; NEURAL NETWORKS; PROTEINS; STRUCTURE (COMPOSITION);

ENZYME INHIBITION;

THROMBIN; TRYPSIN; TRYPSIN INHIBITOR;

ALGORITHM; ARTICLE; CHEMICAL STRUCTURE; CHEMISTRY; DRUG ANTAGONISM; DRUG EFFECT; ENZYME SPECIFICITY; METABOLISM; X RAY CRYSTALLOGRAPHY;

ALGORITHMS; CRYSTALLOGRAPHY, X-RAY; MODELS, MOLECULAR; SUBSTRATE SPECIFICITY; THROMBIN; TRYPSIN; TRYPSIN INHIBITORS;

EID: 5444233141     PISSN: 00952338     EISSN: None     Source Type: Journal    
DOI: 10.1021/ci0401017     Document Type: Article

References (72)

1. Gubernator, K.; Bohm, H. J. In Structure-based Ligand Design; Gubemator, K., Bohm, H. J., Eds.; Methods and Principles in Medicinal Chemistry, Vol. 6; Wiley-VCH: Weinheim, Germany, 1998; pp 1-11.
2. Bernstein, F. C.; Koetzle, T. F.; Williams, G. J. B.; et al. Protein Data Bank. Computer-based Archival File for Macromolecular Structures. J. Mol. Biol. 1977, 112, 535-542.
3. Lyne P. D. Structure-based virtual screening: an overview. Drug. Discovery Today 2002, 7, 1047-1055.
4. Stahl, M.; Rayer, M. Detailed Analysis of Scoring Functions for Virtual Screening. J. Med. Chem. 2001, 44, 1035-1042.
5. Ajay; Murcko M. A. Computational Methods to Predict Binding Free Energy in Ligand-Receptor Complexes. J. Med. Chem. 1995, 38, 4953-4967.
6. Rarey, M.; Kramer, B.; Lengauer, T.; Klebe, G. A fast flexible docking method using an incremental construction algorithm. J. Mol. Biol. 1996, 261, 470-489.
7. Kuntz, I. D.; Blaney, J. M.; Oatley, S. J.; Langridge, R.; Ferrin, T. E. A geometric approach to macromolecule-ligand interactions. J. Mol. Biol. 1982, 161, 269-288.
8. Bohm, H. J. Prediction of binding constants of protein ligands: A fast method for the prioritization of hits obtained from de novo dessign or 3D data base search programs. J. Comput.-Aided Mol. Des. 1998, 12, 309-323.
9. Eldridge, M. D.; Murray, C. W.; Auton, T. R.; Paolini, G. V.; Mee, R. P. Empirical scoring functions: The development of a fast empirical scoring function to estimate the binding affinity of ligands in receptor complexes. J. Comput.-Aided Mol. Des. 1997, 11, 425-445.
10. Cramer, R. D.; DePriest, S. A.; Patterson, D. E.; Hecht, P. In The Developing Practice of Comparative Molecular Field Analysis. 3D QSAR in Drug Design Theory, Methods and Applications; Kubinyi, H., Ed.; ESCOM: Leiden, The Netherlands, 1993; pp 443-485.
11. Klebe, G. Comparative molecular similarity indices analyiss: CoMSIA. Perspect. Drug Discovery 1998, 12, 87-104.
12. Gohlke, H.; Klebe, G. DrugScore Meets CoMFA: Adaptation of fields for molecular comparison (AFMoC) or how to tailor knowledge-based pair-potentials to a particular protein. J. Med. Chem. 2002, 45, 4153-4170.
13. Beveridge, D. L.; Di Capua, F. M. In Computer Simulations of Biomolecular Systems; van Gunsteren, W. F., Weiner, P. K., Eds.; ESCOM: Leiden, The Netherlands, 1989; pp 1-26.
14. Williams, D. H.; Cox, J. P. L.; Doig, A. J.; et al. Toward the semiquantitative estimation of binding constants. J. Am. Chem. Soc. 1991, 113, 7020-7030.
15. Kollman, P. A.; Theory of Macromolecule-Ligand Interactions Curr. Opin. Struct. Biol. 1994, 4, 240-245.
16. Mark, A. E.; van Gunsteren, W. F. Decomposition of the Free-Energy of a system interns of specific Interactions-Implications for Theoretical and Experimental Studies J. Mol. Biol. 1994, 240, 167-176.
17. Gohlke, H.; Hendlich, M.; Klebe, G. Knowledge-based Scoring Function to Predict Protein-Ligand Interactions. J. Mol. Biol. 2000, 295, 337-356.
18. Mitchell, J. B. O.; Laskowski, R. A.; Alexander, A.; Thornton, J. M. BLEEP-Potential of Mean Force Describing Protein-Ligand Interactions: I. Generating Potential. J. Comput. Chem. 1999, 20, 1165-1176.
19. DeWitte, R. S.; Shakhnovich, E. I. SMoG: de Novo Design Method Based on Simple, Fast, and Accurate Free Eenergy Estimates. 1. Methodology and Supporting Evidence. J. Am. Chem. Soc. 1996, 118, 11733-11744.
20. Charifson, P. S.; Corkery, J. P.; Murcko, M. A.; Walters, W. P. Consensus Scoring: A Method for Obtaining Improved Hit Rates from Docking Databases of Three-Dimensional Structures into Proteins. J. Med. Chem. 1999, 42, 5100-5109.
21. Muegge, I.; Martin, Y. C. A General and Fast Scoring Function for Protein-Ligand Interactions: A Simplified Potential Approach. J. Med. Chem. 1999, 42, 791-804.
22. Bagdassarian, C. K.; Schramm, V. L.; Schwarty, S. D. Molecular electrostatic potential analysis for enzymatic substrates, competitive inhibitors and transition-state inhibitors. J. Am. Chem. Soc. 1996, 118, 8825-8836.
23. Braunheim, B. B.; Miles, R. W.; Schramm, V. L.; Schwartz, S. D. Prediction of inhibitor binding free energies by quantum neural networks. Nucleoside Analogues binding to Trypanosomal Nucleoside Hydrolase. Biochemistry 1999, 38, 116076-16083.
24. Mlinsek, G.; Novic, M.; Hodoscek, M.; Solmajer, T. Prediction of enzyme binding: human thrombin inhibition study by quantum chemical and artificial intelligence methods based on X-ray structures. J. Chem. Inf. Comput. Sci. 2001, 41, 1286-1294.
25. Rewinkel, J. B. M.; Adang, A. E. P. Strategies and progress towards the ideal orally active thrombin inhibitor. Curr. Pharm. Des. 1999, 5, 1043-1075.
26. Lefkovits, J.; Topol, E. J. Direct thrombin inhibitors in cardiovascular medicine. Circulation 1994, 3, 1522-36.
27. Stubbs, M.; Bode, W. A player of many parts: the spotlight falls on thrombin's structure. Thromb. Res. 1993, 69, 1-58.
28. Stone, S. R.; Tapparelli, C. Thrombin inhibitors as antithrombotic agents: the importance of rapid inhibition. J. Enzyme Inhib. 1995, 9, 3-15.
29. Bode, W.; Mayr, I.; Baumann, U.; Huber, R.; Stone, S. R.; Hofsteenge, J. The refined 1.9 A crystal structure of human alpha-thrombin: interaction with D-Phe-Pro-Arg chloromethylketone and significance of the Tyr-Pro-Pro-Trp insertion segment. EMBO J. 1989, 8, 3467-3475.
30. InsightII, Version 97.0; MSI Inc.: San Diego, CA, 1997.
31. Zupan, J.; Gasteiger, J. Neural Networks in Chemistry and Drug Design; Wiley-VCH: Weinheim, Germany, 1999.
32. Devilers, J. Genetic Algorithms in Molecular Modeling; Academic Press: New York, 1996.
33. Mochalkin, I; Tulinsky, A. Structure of thrombin retro-inhibited with SEL2711 and SEL2770 as they relate to factor Xa binding. Acta Crystallogr., D 1999, 55, 785-793.
34. Banner, D. W.; Hadvary, P. Crystallographic Analysis at 3.0-A Resolution of the Binding to Human Thrombin of Four Active Site-directed Inhibitors. J. Biol. Chem. 1991, 266, 20085-20093.
35. Zega, A.; Mlinšek, G.; Solmajer, T.; Trampuš-Bakija, A.; Stegnar, M.; Urleb, U. Thrombin inhibitors built on an azaphenylalanine scaffold Bioorg. Med. Chem. Lett. 2004, 14, 1563-1567.
36. Peterlin-Masic, L.; Mlinsek, G.; Solmajer, T.; Trampus-Bakija, A.; Stegnar, M.; Kikelj, D. Novel Thrombin Inhibitors Incorporating Non-basic Partially Saturated Heterobicyclic Pl-arginine mimetics. Bioorg. Med. Chem. Lett. 2003, 13, 789-794.
37. De Simone, G.; Balliano, G.; Milla, P.; et al. Human Alpha-Thrombin Inhibition by the Highly Selective Compounds N-ethoxycarbonyl-D-Phe-Pro-alpha- azaLys p-Nitrophenyl Ester and N-carbobenzoxy-Pro-alpha-azaLys p-Nitrophenyl Ester: A Kinetic, Thermodynamic and X-ray Crystallographic Study. J. Mol. Biol. 1997, 269, 558-569.
38. Wagner, J.; Kallen, J.; Ehrhardt, C.; Evenou, J.-P.; Wagner, D. Rational Design, Synthesis, and X-ray Structure of Selective Noncovalent Thrombin Inhibitors. J. Med. Chem. 1998, 41, 3664-3674.
39. Krishnan, R.; Mochalkin, I.; Ami, R.; Tulinsky A. Structure of thrombin complexed with selective non-electrophilic inhibitors having cyclohexyl moieties at Pl. Acta Crystallogr., D 2000, 56, 294-303.
40. Katz, B. A.; Mackman, R.; Luong, C.; et al. Structural Basis for Selectivity of a Small Molecule, S1-Binding, Submicromolar Inhibitor of Urokinase-Type Plasminogen Activator. Chem. Biol. 2000, 7, 299-306.
41. Matthews, J. H.; Krishnan, R.; Costanzo, M. J.; Maryanoff, B. E.; Tulinsky, A. Crystal Structures of Thrombin with Thiazole-Containing Inhibitors: Probes of the S1 Binding Site. Biophys. J. 1996, 71, 2830-2839.
42. Malley, M. F.; Tabernero, L.; Chang, C. Y.; et al. Crystallographic determination of the structures of human alpha-thrombin complexed with BMS-186282 and BMS-189090. Protein Sci. 1996, 5, 221-228.
43. Tabernero, L.; Chang, C. Y. Y.; Ohringer, S. L.; et al. Structure of a Retro-binding Peptide Inhibitor Complexed with Human Alpha-Thrombin. J. Mol. Biol. 1995, 246, 14-20.
44. Peterlin-Masic, L.; Kranjc, A.; Mlinsek, G.; Solmajer, T.; Stegnar, M.; Kikelj D. Selective 3-Amino-2-Pyridinone Acetamide Thrombin Inhibitors Incorporating Weakly Basic Partially Saturated Heterobicyclic Pl-Arginine Mimetics. Bioorg. Med. Chem. Lett. 2003, 13, 3171-3179.
45. Marinko, P.; Krbavcic, A.; Mlinsek, G.; Šolmajer, T.; Trampuš Bakija, A.; Stegnar, M.; Stojan, J.; Kikelj. D. Novel non-covalent thrombin inhibitors incorporating PI 4,5,6,7-tetrahydobenzothiazole arginine mimetics. Eur. J. Med. Chem. 2004, 39, 257-265.
46. Banner, D. W. Private communication.
47. Conti, E.; Rivetti, C.; Wonacott, A.; Brick, P. X-ray and spectrophotometric studies of the binding of proflavin to the S1 specificity pocket of human alpha-thrombin. FEBS Lett. 1998, 425, 229-233.
48. Bone, R.; Lu, T.; Illig, C. R.; Soil, R. M.; Spurlino, J. C. Structural Analysis of Thrombin Complexed with Potent Inhibitors Incorporating a Phenyl Group as a Peptide Mimetic and Aminopyridines as Guanidine Substitutes. J. Med. Chem. 1998, 41, 2068-2075.
49. Lyle, T. A.; Chen, Z. G.; Appleby, S. D.; et al. Synthesis, evaluation, and Crystallographic analysis of L-371, 912: A potent and selective active-site thrombin inhibitor. Bioorg. Med. Chem. Lett. 1997, 7, 67-72.
50. Dullweber, F.; Stubbs, M. T.; Musil, D.; Sturzebecher, J.; Klebe, G. Factorising Ligand Affinity: A Combined Thermodynamic and Crystallographic Study of Trypsin and Thrombin Inhibition. J. Mol Biol. 2001, 313, 593-614.
51. Katz, B. A.; Clark, J. M.; Finer-Moore, J. S.; et al. Design of potent selective zinc-mediated serine protease inhibitors. Nature 1998, 391, 608-612.
52. Katz, B. A.; Elrod, K.; Luong, C.; et al. A Novel Serine Protease Inhibition Motif Involving a Multi-centered Short Hydrogen Bonding Network at the Active Site. J. Mol. Biol. 2001, 307, 1451-1486.
53. Steiner, J. L. R.; Murakami, M.; Tulinsky A. Structure of Thrombin Inhibited by Aeruginosin 298-A from a Blue-Green Alga. J. Am. Chem. Soc. 1998, 120, 597-598.
54. Hauel, N.; Nar, H.; Priepke, H.; Ries, U.; Stassen, J. M.; Wienen, W. Structure-Based Design of Novel Potent Nonpeptide Thrombin Inhibitors. J. Med. Chem. 2002, 45, 1757-1766.
55. Stubbs, M. T.; Huber, R.; Bode W. Crystal structures of factor Xa specific inhibitors in complex with trypsin: structural grounds for inhibition of factor Xa and selectivity against thrombin. FEBS Lett. 1995, 375, 103-107.
56. Maignan, S.; Guilloteau, J. P.; Pozieux, S.; et al. Crystal Structures of Human Factor Xa Complexed with Potent Inhibitors. J. Med. Chem. 2000, 43, 3226-3232.
57. Presnell, S. R.; Patil, G. S.; Mura, C.; et al. Oxyanion-Mediated Inhibition of Serine Proteases. Biochemistry 1998, 37, 17068-17081.
58. Maduskuie, T. P.; McNamara, K. J.; Ru, Y.; Knabb, R. M.; Stouten, P. F. W. Rational design and synthesis of novel, potent bisphenylamidine carboxylate factor Xa inhibitors J. Med. Chem. 1998, 41, 53-62.
59. Kurinov, I. V.; Harrison, R. W. Prediction of new serine proteinase inhibitors. Nat. Struct. Biol. 1994, 1, 735-743.
60. Ota, N.; Stroupe, C.; Ferreira-da-Silva, J. M. S.; Shah, S. A.; Mares-Guia M. Non-Boltzmann Thermodynamic Integration (NBTI) for Macromolecular Systems: Relative Free Energy of Binding of Trypsin to Benzamidine and Benzylamine. Proteins: Struct., Funct., Genet. 1999, 37, 641-653.
61. Nar, H.; Bauer, M.; Schmid, A.; et al. Structural basis for Inhibition Promisuity of Dual Specific Thrombin and Factor Xa Blood Coagulation Inhibitors. Structure 2001, 9, 29.
62. Turk, D.; Sturzebecher, J.; Bode W. Geometry of binding of the N alpha-tosylated piperidides of m-amidino-, p-amidino- and p-guanidino phenylalanine to thrombin and trypsin. X-ray crystal structures of their trypsin complexes and modeling of their thrombin complexes. FEBS Lett. 1991, 287, 133-138.
63. Liebeschuetz, J. W.; Jones, S. D.; Morgan, P. J.; et al. PRO_SELECT: Combining Structure-Based Drug Design and Array-Based Chemistry for Rapid Lead Discovery. 2. The Development of a Series of Highly Potent and Selective Factor Xa Inhibitors. J. Med. Chem. 2002, 45, 1221-1232.
64. Bode, W.; Turk, D.; Sturzebecher, J. Geometry of binding of the benzamidine- and arginine-based inhibitors N alpha-(2-naphthyl-sulphonyl-glycyl) -DL-p-amidinophenylalanyl-pipe ridine (NAPAP) and (2R,4R)-4-methyl-1-[N alpha-(3-methyl-1,2,3,4-tetrahydro-8- quinolinesulphonyl)-L-arginyl]-2- piperidine carboxylic acid (MQPA) to human alpha-thrombin. X-ray crystallographic determination of the NAPAP-trypsin complex and modeling of NAPAP-thrombin and MQPA-thrombin. Eur. J. Biochem. 1990, 193, 175-182.
65. Katz, B. A.; Finer-Moore, J.; Mortezaei, R.; Rich, D. H.; Stroud, R. M. Episelection: Novel Ki Nanomolar Inhibitors of Serine Proteases Selected by Binding or Chemistry on an Enzyme Surface. Biochemistry 1995, 34, 8264-8280.
66. Lee, A. Y.; Smitka, T. A.; Bonjouklian, R.; Clardy, J. Atomic structure of the trypsin-A90720A complex: a unified approach to structure and function. Chem. Biol. 1994, 1, 113-117.
67. Sandler, B.; Murakami, M.; Clardy J. Atomic Structure of Trypsin-Aeruginosin 98B Complex. J. Am. Chem. Soc. 1998, 120, 595-596.
68. References to the Brookhaven PDB and additional descriptors are available as Supporting Information.
69. Figures illustrating the results of the CP-ANN model for the training - test set are available as Supporting Information.
70. Stubbs, M. T.; Reyda, S.; Dullweber, F.; et al. pH-Dependent binding modes observed in trypsin crystals: lessons for structure-based drug design. ChemBioChem 2002, 3, 246-249.
71. Davis, A. M.; Teague, S. J. Hydrophobic Interactions and Failure of the Rigid Receptor Hypothesis. Angew. Chem. 1999, 38, 736-749.
72. Klon, A. E.; Glick, M.; Thoma, M.; Acklin, P.; Davies, J. W. Finding More Needles in the Haystack: A Simple and Efficient Method for Improving High-Throughput Docking Results J. Med. Chem. 2004, 47, 2743-2749.