Why pyridine containing pyrido[2,3-d]pyrimidin-7-ones selectively inhibit CDK4 than CDK2: Insights from molecular dynamics simulation

Journal of Molecular Graphics and Modelling

Volumn 28, Issue 7, 2010, Pages 695-706

  Mascarenhas, Nahren Manuel ^a   Bhattacharyya, Dhananjay ^b   Ghoshal, Nanda ^a  

^a INDIAN INSTITUTE OF CHEMICAL BIOLOGY   (India)

^b SAHA INSTITUTE OF NUCLEAR PHYSICS   (India)

Author keywords

CDK2; CDK4; Ligand binding; Molecular dynamics; Selectivity

Indexed keywords

ACTIVE CENTER; ACTIVE SITE; ANTICANCER DRUG; BINDING INTERACTION; CDK2; CONFORMATIONAL CHANGE; CYCLIN-DEPENDENT KINASE; HYDROGEN BONDINGS; LIGAND BINDING; MOLECULAR BASIS; MOLECULAR DYNAMICS SIMULATIONS; POSITIVE CHARGES; PROTEIN-LIGAND INTERACTIONS; PYRIDINE NITROGEN; SELECTIVE INHIBITION; WATER MOLECULE;

BINDING ENERGY; DYNAMICS; HYDROGEN BONDS; LIGANDS; MOLECULAR DYNAMICS; MOLECULAR MECHANICS; PROTEINS; PYRIDINE;

PRINCIPAL COMPONENT ANALYSIS;

CYCLIN DEPENDENT KINASE 2; CYCLIN DEPENDENT KINASE 4; PYRIDINE; PYRIDO [2,3, DEXTRO]PYRIMIDIN 7 ONE; UNCLASSIFIED DRUG;

ARTICLE; BINDING AFFINITY; BINDING SITE; CHEMICAL STRUCTURE; CONFORMATIONAL TRANSITION; CONTROLLED STUDY; CRYSTALLOGRAPHY; ELECTRIC POTENTIAL; HYDROGEN BOND; HYDROPHOBICITY; LIGAND BINDING; MOLECULAR DYNAMICS; PRINCIPAL COMPONENT ANALYSIS; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN FOLDING; PROTEIN INTERACTION;

CYCLIN-DEPENDENT KINASE 2; CYCLIN-DEPENDENT KINASE 4; HYDROGEN BONDING; LIGANDS; MOLECULAR DYNAMICS SIMULATION; PRINCIPAL COMPONENT ANALYSIS; PROTEIN STRUCTURE, SECONDARY; PYRIMIDINONES; STATIC ELECTRICITY; STRUCTURAL HOMOLOGY, PROTEIN; SUBSTRATE SPECIFICITY;

EID: 76749086536     PISSN: 10933263     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.jmgm.2010.01.008     Document Type: Article

References (56)

1. Collins K.J.T., and Pavletich N.P. The cell cycle and cancer. Proc. Natl. Acad. Sci. U.S.A. 94 (1997) 2776-2778
2. Morgan D. Cyclin-dependent kinases: engines, clocks, and microprocessors. Annu. Rev. Cell Dev. Biol. 13 (1997) 261-291
3. Kasten M.M., and Giordano A. pRb and the cdks in apoptosis and the cell cycle. Cell Death Differ. 5 (1998) 132-140
4. Ortega S., Malumbres M., and Barbacid M. Cyclin D-dependent kinases, INK4 inhibitors and cancer. Biochim. Biophys. Acta 1602 (2002) 73-87
5. Ortega S., Malumbres M., and Barbacid M. Cell cycle and cancer: the G1 restriction point and the G1/S transition. Curr. Genomic. 3 (2002) 245-263
6. Landis M.W., Pawlyk B.S., Li T., Sicinski P., and Hinds P.W. Cyclin D1-dependent kinase activity in murine development and mammary tumorigenesis. Cancer Cell 9 (2006) 13-22
7. Yu Q., Sicinska E., Geng Y., Ahnstrom M., Zagozdzon A., Kong Y., Gardner H., Kiyokawa H., Harris L.N., Stal O., and Sicinski P. Requirement for CDK4 kinase function in breast cancer. Cancer Cell 9 (2006) 23-32
8. Sridhar P., Akula N., and Pattabiraman N. Selectivity and potency of cyclin-dependent kinase inhibitors. AAPS J. 8 (2006) E204-E221
9. Honma T., Yoshizumi T., Hashimoto N., Hayashi K., Kawanishi N., Fukasawa K., Takaki T., Ikeura C., Ikuta M., Suzuki-Takahashi I., Hayama T., Nishimura S., and Morishima H. A novel approach for the development of selective CDK4 inhibitors: library design based on locations of CDK4 specific amino acid residues. J. Med. Chem. 44 (2001) 4628-4640
10. McInnes C., Wang S., Anderson S., O'Boyle J., Jackson W., Kontopidis G., Meades C., Mezna M., Thomas M., Wood G., Lane D.P., and Fischer P.M. Structural determinants of cdk4 inhibition and design of selective ATP competitive inhibitors. Chem. Biol. 11 (2004) 525-534
11. Rossi K.A., Markwalder J.A., Seitz S.P., Chang C.H., Cox S., Boisclair M.D., Brizuela L., Brenner S.L., and Stouten P.F. Understanding and modulating cyclin-dependent kinase inhibitor specificity: molecular modeling and biochemical evaluation of pyrazolopyrimidinones as CDK2/cyclin A and CDK4/cyclin D1 inhibitors. J. Comput. Aided Mol. Des. 19 (2005) 111-122
12. Park H., Yeom M.S., and Lee S. Loop flexibility and solvent dynamics as determinants for the selective inhibition of cyclin-dependent kinase 4: comparative molecular dynamics simulation studies of CDK2 and CDK4. Chembiochem 5 (2004) 1662-1672
13. Jiang Y., Zou J., and Gui C. Study of a ligand complexed with CDK2/CDK4 by computer simulation. J. Mol. Model. 11 (2005) 509-515
14. Dasselew N., and Bharatam P.V. 3D-QSAR and molecular docking study on bisarylmaleimide series as glycogen synthase kinase 3, cyclin dependent kinase 2 and cyclin dependent kinase 4 inhibitors: an insight into the criteria for selectivity. Eur. J. Med. Chem. 42 (2007) 1014-1027
15. Pratt D.J., Bentley J., Jewsbury P., Boyle F.T., Endicott J.A., and Noble M.E. Dissecting the determinants of cyclin-dependent kinase 2 and cyclin-dependent kinase 4 inhibitor selectivity. J. Med. Chem. 49 (2006) 5470-5477
16. Day P.J., Cleasby A., Tickle I.J., O'Reilly M., Coyle J.E., Holding F.P., McMenamin R.L., Yon J., Chopra R., Lengauer C., and Jhoti H. Crystal structure of human CDK4 in complex with a D-type cyclin. Proc. Natl. Acad. Sci. U.S.A. 106 (2009) 4166-4170
17. Takaki T., Echalier A., Brown N.R., Hunt T., Endicott J.A., and Noble M.E. The structure of CDK4/cyclin D3 has implications for models of CDK activation. Proc. Natl. Acad. Sci. U.S.A. 106 (2009) 4171-4176
18. Toogood P.L., Harvey P.J., Repine J.T., Sheehan D.J., Wel S.N.V., Zhou H., Keller P.R., McNamara D.J., Sherry D., Zhu T., Brodfuehrer J., Choi C., Barvian M.R., and Fry D.W. Discovery of a potent and selective inhibitor of cyclin-dependent kinase 4/6. J. Med. Chem. 48 (2005) 2388-2406
19. Berman H.M., Westbrook J., Feng Z., Gilliland G., Bhat T.N., Weissig H., Shindyalov I.N., and Bourne P.E. The protein data bank. Nucleic Acids Res. 28 (2000) 235-242
20. Jeffrey P.D., Russo A.A., Polyak K., Gibbs E., Hurwitz J., Massague J., and Pavletich N.P. Mechanism of CDK activation revealed by the structure of a cyclinA-CDK2 complex. Nature 376 (1995) 313-320
21. Mascarenhas N.M., and Ghoshal N. Combined ligand and structure based approaches for narrowing on the essential physicochemical characteristics for CDK4 inhibition. J. Chem. Inf. Model. 48 (2008) 1325-1336
22. Lu H., and Schulze-Gahmen U. Toward understanding the structural basis of cyclin-dependent kinase 6 specific inhibition. J. Med. Chem. 49 (2006) 3826-3831
23. Laskowski R.A., MacArthur M.W., Moss D.S., and Thornton J.M. PROCHECK: a program to check the stereochemical quality of protein structures. J. Appl. Cryst. 26 (1993) 283-291
24. Jones G., Willett P., Glen R.C., Leach A.R., and Taylor R. Development and validation of a genetic algorithm for flexible docking. J. Mol. Biol. 267 (1997) 727-748
25. Eldridge M.D., Murray C.W., Auton T.R., Paolini G.V., and Mee R.P. Empirical scoring functions: I. The development of a fast empirical scoring function to estimate the binding affinity of ligands in receptor complexes. J. Comput. Aided Mol. Des. 11 (1997) 425-445
26. Van Der Spoel D., Lindahl E., Hess B., Groenhof G., Mark A.E., and Berendsen H.J. GROMACS: fast, flexible, and free. J. Comput. Chem. 26 (2005) 1701-1718
27. Schuttelkopf A.W., and van Aalten D.M. PRODRG: a tool for high-throughput crystallography of protein-ligand complexes. Acta Crystallogr. D Biol. Crystallogr. 60 (2004) 1355-1363
28. Schmidt M.W., Baldridge K.K., Boatz J.A., Elbert S.T., Gordaon M.S., Jensen J.H., Koseki S., Nguyen K.A., Su S., Windus T.L., Dupius M., and Montgomery J.A. General atomic and molecular electronic structure systems. J. Comput. Chem. 14 (1993) 1347-1363
29. Senda, N. http://winmostar.com/help_en.html.
30. Hess B., Bekker H., Berendsen H.J.C., and Fraaije J.G.E.M. LINCS: A linear constraint solver for molecular simulations. J. Comp. Chem. 18 (1997) 1463-1472
31. Berendsen H.J.C., Postma J.P.M., van Gunsteren W.F., Dinola A., and Haak J.R. Molecular-dynamics with coupling to an external bath. J. Chem. Phys. 81 (1984) 3684-3690
32. Parrinello M., and Rahman A. Polymorphic transitions in single crystals: A new molecular dynamics method. J. Appl. Phys. 52 (1981) 7182-7190
33. Humphrey W., Dalke A., and Schulten K. VMD: visual molecular dynamics. J. Mol. Graph. 14 (1996) 33-38
34. Gilson M., Sharp K., and Honig B. Calculating electrostatic interactions in bio-molecules: Method and error assessment. J. Comp. Chem. 9 (1988) 327-335
35. Amadi A., Linssen A.B.M., and Berendsen H.J.C. Essential dynamics of proteins. Proteins 17 (1993) 412-425
36. Otyepka M., Kríz Z., and Koca J. Dynamics and binding modes of free CDK2 and its two complexes with inhibitors studied by computer simulations. J. Biomol. Struct. Dyn. 20 (2002) 141-154
37. Kabsch W., and Sander C. Dictionary of protein secondary structure: pattern recognition of hydrogen-bonded and geometrical features. Biopolymers 22 (1983) 2577-2637
38. De Bondt H.L., Rosenblatt J., Jancarik J., Jones H.D., Morgan D.O., and Kim S.H. Crystal structure of cyclin-dependent kinase 2. Nature 363 (1993) 595-602
39. Lolli G., Lowe E.D., Brown N.R., and Johnson L.N. The crystal structure of human CDK7 and its protein recognition properties. Structure 12 (2004) 2067-2079
40. Brotherton D.H., Dhanaraj V., Wick S., Brizuela L., Domaille P.J., Volyanik E., Xu X., Parisini E., Smith B.O., Archer S.J., Serrano M., Brenner S.L., Blundell T.L., and Laue E.D. Crystal structure of the complex of the cyclinD-dependent kinase CDK6 bound to the cell-cycle inhibitor p19INK4d. Nature 395 (1998) 244-250
41. Schulze-Gahmen U., De Bondt H.L., and Kim S.H. High-resolution crystal structures of human cyclin-dependent kinase 2 with and without ATP: bound waters and natural ligand as guides for inhibitor design. J. Med. Chem. 39 (1996) 4540-4546
42. Radzio-andzelm E., Lew J., and Taylor S. Bound to activate: conformational consequences of cyclin binding to CDK2. Curr. Biol. 3 (1995) 1135-1141
43. Davies T.G., Pratt D.J., Endicott J.A., Johnson L.N., and Noble M.E. Structure-based design of cyclin-dependent kinase inhibitors. Pharmacol. Ther. 93 (2002) 125-133
44. Lu H., Chang D.J., Baratte B., Meijer L., and Schulze-Gahmen U. Crystal structure of a human cyclin-dependent kinase 6 complex with a flavonol inhibitor, fisetin. J. Med. Chem. 48 (2005) 737-743
45. Welburn J.P.I., Tucker J.A., Johnson T., Lindert L., Morgan M., Willis A., Noble M.E.M., and d'Endicott J.A. How tyrosine 15 phosphorylation inhibits the activity of cyclin-dependent kinase 2-cyclin A. J. Biol. Chem. 282 (2007) 3173-3181
46. Bartova I., Otyepka M., Kriz Z., and Koca J. Activation and inhibition of cyclin-dependent kinase-2 by phosphorylation; a molecular dynamics study reveals the functional importance of the glycine-rich loop. Protein Sci. 13 (2004) 1449-1457
47. Davies T.G., Bentley J., Arris C.E., Boyle F.T., Curtin N.J., Endicott J.A., Gibson A.E., Golding B.T., Griffin R.J., Hardcastle I.R., Jewsbury P., Johnson L.N., Mesguiche V., Newell D.R., Noble M.E., Tucker J.A., Wang L., and Whitfield H.J. Structure-based design of a potent purine-based cyclin-dependent kinase inhibitor. Nat. Struct. Biol. 9 (2002) 745-749
48. Scheiner S., Kar T., and Pattanayak J. Comparison of various types of hydrogen bondsinvolving aromatic amino acids. J. Am. Chem. Soc. 124 (2002) 13257-13264
49. Jain A., Ramanathan V., and Sankararamakrishnan R. Lone pair . pi interactions between water oxygens and aromatic residues: quantum chemical studies based on high-resolution protein structures and model compounds. Protein Sci. 18 (2009) 595-605
50. Zhang B., Tan V.B., Lim K.M., and Tay T.E. Significance of water molecules in the inhibition of cyclin-dependent kinase 2 and 5 complexes. J. Chem. Inf. Model. 47 (2007) 1877-1885
51. Kríz Z., Otyepka M., Bártová I., and Koca J. Analysis of CDK2 active-site hydration: a method to design new inhibitors. Proteins 55 (2004) 258-274
52. Finlay M.R., Acton D.G., Andrews D.M., Barker A.J., Dennis M., Fisher E., Graham M.A., Green C.P., Heaton D.W., Karoutchi G., Loddick S.A., Morgentin R., Roberts A., Tucker J.A., and Weir H.M. Imidazole piperazines: SAR and development of a potent class of cyclin-dependent kinase inhibitors with a novel binding mode. Bioorg. Med. Chem. Lett. 18 (2008) 4442-4446
53. De Azevedo W.F., Mueller-Dieckmann H.J., Schulze-Gahmen U., Worland P.J., Sausville E., and Kim S.H. Structural basis for specificity and potency of a flavonoid inhibitor of human CDK2. a cell cycle kinase. Proc. Natl. Acad. Sci. U.S.A. 93 (1996) 2735-2740
54. Meijer L. Chemical inhibitors of cyclin-dependent kinases. Trends Cell Biol. 6 (1996) 393-397
55. Russo A.A., Jeffrey P.D., and Pavletich N.P. Structural basis of cyclin-dependent kinase activation by phosphorylation. Nat. Struct. Biol. 3 (1996) 696-700
56. Bártová I., Koca J., and Otyepka M. Functional flexibility of human cyclin-dependent kinase-2 and its evolutionary conservation. Protein Sci. 17 (2008) 22-33