Molecular modeling and molecular dynamics simulation studies on pyrrolopyrimidine-based α-helix mimetic as dual inhibitors of MDM2 and MDMX

Journal of Molecular Graphics and Modelling

Volumn 30, Issue , 2011, Pages 167-178

  Lu, Shao Yong ^a   Jiang, Yong Jun ^b   Zou, Jian Wei ^b   Wu, Tian Xing ^a  

^a ZHEJIANG UNIVERSITY   (China)

^b ZHEJIANG UNIVERSITY   (China)

Author keywords

MDM2; MDMX; Molecular docking; Molecular dynamics simulations; P53

Indexed keywords

BINS; FREE ENERGY; MOLECULAR DYNAMICS; MOLECULAR MODELING; PROTEINS; VAN DER WAALS FORCES;

GENERALIZED BORN/SURFACE AREA; MDM2; MDMX; MOLECULAR DOCKING; MOLECULAR DYNAMICS SIMULATIONS; SHAPE COMPLEMENTARITY; TUMOR SUPPRESSOR PROTEINS; VAN DER WAALS ENERGIES;

BINDING ENERGY;

NC 1; PROTEIN MDM2; PROTEIN MDMX; PROTEIN P53; PYRROLOPYRIMIDINE DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; BINDING AFFINITY; CHEMICAL REACTION; CHEMICAL STRUCTURE; LIGAND BINDING; MOLECULAR DOCKING; MOLECULAR DYNAMICS; MOLECULAR MECHANICS; MOLECULAR MODEL; PRIORITY JOURNAL; PROTEIN PROTEIN INTERACTION; SIMULATION; SPATIAL ORIENTATION; SURFACE PROPERTY; VAN DER WAALS;

EID: 84855299549     PISSN: 10933263     EISSN: 18734243     Source Type: Journal    
DOI: 10.1016/j.jmgm.2011.07.003     Document Type: Article

References (71)

1. B. Vogelstein, D. Lane, A. Levine, Surfing the p53 network, Nature 408 (2000) 307-310.
2. F. Toledo, G.M.Wahl, Regulating the p53 pathway: in vitro hypotheses, in vivo veritas, Nat. Rev. Cancer 6 (2006) 909-923. (Pubitemid 44862676)
3. K.H. Vousden, D.P. Lane, P53 in health and disease, Nat. Rev. Mol. Cell Biol. 8 (2006) 275-283. (Pubitemid 46474662)
4. M. Hollstein, D. Sidransky, B. Volgelstein, C.C. Harris, P53 mutations in human cancers, Science 253 (1990) 49-53. (Pubitemid 21917115)
5. A.C. Joerger, A.R. Fersht, Structural biology of the tumor suppressor p53, Annu. Rev. Biochem. 77 (2008) 557-582.
6. Y. Haupt, R. Maya, A. Kazaz, M. Oren, Mdm2 promotes the rapid degradation of p53, Nature 387 (1997) 296-299. (Pubitemid 27220766)
7. M.H. Kubbutat, S.N. Jones, K.H. Vousden, Regulation of p53 stability by Mdm2, Nature 387 (1997) 299-303. (Pubitemid 27220767)
8. J.C. Marine, M.A. Dyer, A.G. Jochemsen, Inactivation of the p53 pathway in retinoblastomas, J. Cell Sci. 120 (2007) 371-378.
9. M. Wade, G.M. Wahl, Targeting Mdm2 and Mdmx in cancer therapy: better living through medicinal chemistry? Mol. Cancer Res. 7 (2009) 1-11.
10. P.H. Kussie, S. Gorina, V. Marechal, B. Elenbaas, J. Moreau, A.J. Levine, N.P. Pavletich, Structure of the MDM2 oncoprotein bound to the p53 tumor suppressor transactivation domain, Science 274 (1996) 948-953. (Pubitemid 26398409)
11. J.D. Oliner, J.A. Pietenpol, S. Thiagalingam, J. Gyuris, K.W. Kinzler, B. Vogelstein, Oncoprotein MDM2 conceals the activation domain of tumor suppressor p53, Nature 362 (1993) 857-860. (Pubitemid 23132165)
12. G.M. Popowicz, A. Czarna, T.A. Holak, Structure of the human Mdmx protein bound to the p53 tumor suppressor transactivation domain, Cell Cycle 7 (2008) 2441-2443.
13. J.D. Oliner, K.W. Kinzler, P.S. Meltzer, D.L. George, B. Vogelstein, Amplification of a gene encoding a p53-associated protein in human sarcomas, Nature 358 (1992) 80-83.
14. Y.F. Ramos, R. Stad, J. Attema, L.T. Peltenburg, A.J. van der Eb, A.G. Jochemsen, Aberrant expression ofHDMXproteins in tumor cells correlates with wild-type p53, Cancer Res. 61 (2001) 1839-1842. (Pubitemid 32691995)
15. N.A. Laurie, S.L. Donovan, C.S. Shih, J. Zhang, N. Mills, C. Fuller, A. Teunisse, S. Lam, Y. Ramos, A. Mohan, D. Johnson, M. Wilson, C. Rodriguez-Galindo, M. Quarto, S. Francoz, S.M. Mendrysa, R.K. Guy, J.C. Marine, A.G. Jochemsen, M.A. Dyer, Inactivation of the p53 pathway in retinoblastoma, Nature 444 (2006) 61-66. (Pubitemid 44684754)
16. C. Li, M. Pazgier, C. Li, W. Yuan, M. Liu, G. Wei, W.Y. Lu, W. Lu, Systematic mutational analysis of peptide inhibition of the p53-MDM2/MDMX interactions, J. Mol. Biol. 398 (2010) 200-213.
17. K. Barakat, J. Mane, D. Friesen, J. Tuszynski, Ensemble-based virtual screening reveals dual-inhibitors for the p53-MDM2/MDMX interactions, J. Mol. Graph. Model. 28 (2010) 555-568.
18. J. Chen, J. Wang, B. Xu, W. Zhu, G. Li, Insights into mechanism of small molecule inhibitors of the MDM2-p53 interaction: molecular dynamics simulation and free energy analysis, J. Mol. Graph. Model. (2011), doi:10.1016/j.jmgm.2011. 06.003.
19. G. Hu, D. Wang, X. Liu, Q. Zhang, A computational analysis of the binding model of MDM2 with inhibitors, J. Comput. Aided Mol. Des. 24 (2010) 687-697.
20. A. Czarna, G.M. Popowicz, A. Pecak, S. Wolf, G. Dubin, T.A. Holak, High affinity interaction of the p53 peptide-analogue with human Mdm2 and Mdmx, Cell Cycle 8 (2009) 1176-1184.
21. M. Liu, C. Li, M. Pazgier, C. Li, Y. Mao, Y. Lv, B. Gu, G. Wei, W. Yuan, C. Zhan, W.Y. Lu, W. Lu, D-peptide inhibitors of the p53-MDM2 interaction for targeted molecular therapy of malignant neoplasms, Proc. Natl. Acad. Sci. U.S.A. 107 (2010) 14321-14326.
22. C. Garcia-Echeverria, P. Chène, M.J.J. Blommers, P. Furet, Discovery of potent antagonists of the interaction between human double minute 2 and tumor suppressor p53, J. Med. Chem. 43 (2000) 3205-3208.
23. A. Böttger, V. Böttger, S.F. Howard, S.M. Picksley, P. Chène, C. Garcia-Echeverria, H.K. Hochkeppel, D.P. Lane, Identification of novel mdm2 binding peptides by phage display, Oncogene 13 (1996) 2141-2147. (Pubitemid 26411564)
24. L.T. Vassilev, B.T. Vu, B. Graves, D. Carvajal, F. Podlaski, Z. Filipovic, N. Kong, U. Kammlott, C. Lukacs, C. Klein, N. Fotouhi, E.A. Liu, In vivo activation of the p53 pathway by small-molecule antagonists of MDM2, Science 303 (2004) 844-848. (Pubitemid 38174664)
25. B.L. Grasberger, T. Lu, C. Schubert, D.J. Parks, T.E. Carver, H.K. Koblish, M.D. Cummings, L.V. LaFrance, K.L. Milkiewicz, R.R. Calvo, D. Maguire, J. Lattanze, C.F. Franks, S. Zhao, K. Ramachandren, G.R. Bylebyl, M. Zhang, C.L. Manthey, E.C. Petrella, M.W. Pantoliano, I.C. Deckman, J.C. Spurlino, A.C. Maroney, B.E. Tomczuk, C.J. Molloy, R.F. Bone, Discovery and cocrystal structure of benzodiazepinedione HDM2 antagonists that activate p53 in cells, J. Med. Chem. 48 (2005) 909-912. (Pubitemid 40270436)
26. K. Ding, Y. Lu, Z. Nikolovska-Coleska, G. Wang, S. Qiu, S. Shangary, W. Gao, D. Qin, J. Stuckey, K. Krajewski, P.P. Roller, S. Wang, Structure-based design of spiro-oxindoles as potent, specific small-molecule inhibitors of theMDM2-p53 interaction, J. Med. Chem. 49 (2006) 3432-3435. (Pubitemid 43902447)
27. I.R. Hardcastle, J. Liu, E. Valeur, A. Watson, S.U. Ahmed, T.J. Blackburn, K. Bennaceur, W. Clegg, C. Drummond, J.A. Endicott, B.T. Golding, R.J. Griffin, J. Gruber, K. Haggerty, R.W. Harrington, C. Hutton, S. Kemp, X. Lu, J.M. McDonnell, D.R. Newell, M.E.M. Noble, S.L. Payne, C.H. Revill, C. Riedinger, Q. Xu, J. Lunec, Isoindolinone inhibitors of murine double minute 2 (MDM2)-p53 protein-protein interaction: structure-activity studies leading to improved potency, J. Med. Chem. 54 (2011) 1233-1243.
28. M. Pazgier, M. Liu, G. Zou, W. Yuan, C. Li, C. Li, J. Monbo, D. Zella, S.G. Tarasov, W. Lu, Structural basis for high-affinity peptide inhibition of p53 interactions with MDM2 and MDMX, Proc. Natl. Acad. Sci. U.S.A. 106 (2009) 4665-4670.
29. C. Li, M. Pazgier, M. Liu, W.Y. Lu, W. Lu, Apamin as template for structure-based rational design of potent peptide activators of p53, Angew. Chem. Int. Ed. 48 (2009) 8712-8715.
30. M.P. Dickens, R. Fitzgerald, P.M. Fischer, Small-molecule inhibitors of MDM2 as new anticancer therapeutics, Semin. Cancer Biol. 20 (2010) 10-18.
31. G.M. Popowicz, A. Czarna, U. Rothweiler, A. Szwagierrczak, M. Krajewski, L. Weber, T.A. Holak, Molecular basis for the inhibition of p53 by Mdmx, Cell Cycle 6 (2007) 2386-2392. (Pubitemid 350064092)
32. A. Macchiarulo, N. Giacchè, A. Carotti, M. Baroni, G. Cruciani, R. Pellicciari, Targeting the conformational transitions of MDM2 and MDMX: insights into dissimilarities and similarities of p53 recognition, J. Chem. Inf. Model. 48 (2008) 1999-2009.
33. A. Carotti, A. Macchiarulo, N. Giacchè, R. Pellicciari, Targeting the conformational transitions of MDM2 and MDMX: insights into key residues affecting p53 recognition, Proteins 77 (2009) 524-535.
34. L.M. Fonseca-Espinoza, J.G. Ferrara-Trujillo, Conformational changes of the p53-binding cleft of MDM2 revealed by molecular dynamics simulations, Biopolymers 83 (2006) 365-373.
35. S.G. Dastidar, D.P. Lane, C.S. Verma, Modulation of p53 binding to MDM2: computational studies reveal important roles of Tyr100, BMC Bioinformatics 10 (2009) S6.
36. G.M. Popowicz, A. Czarna, S. Wolf, K. Wang, W. Wang, A. Dömling, T.A. Holak, Structure of low molecular weight inhibitors bound to MDMX and MDM2 reveal new approaches for p53-MDMX/MDM2 antagonist drug discovery, Cell Cycle 9 (2010) 1104-1111.
37. J.H. Lee, Q. Zhang, S. Jo, S.C. Chai, M. Oh, W. Im, H. Lu, H.S. Lim, Novel pyrrolopyrimidine-based α-helix mimetics: cell-permeable inhibitors of protein-protein interactions, J. Am. Chem. Soc. 133 (2011) 676-679.
38. Sybyl Version 6.8, Tripos Associates Inc., St. Louis, MO, 2001.
39. G.M. Morris, R. Huey, W. Lindstrom, M.F. Sanner, R.K. Belew, D.S. Goodsell, A.J. Olson, Autodock4 and AutoDockTools4: automated docking with selective receptor flexibility, J. Comput. Chem. 30 (2009) 2785-2791.
40. H.K. Srivastava, M. Chourasia, D. Kumar, G.N. Sastry, Comparison of computational methods to model DNA minor groove binders, J. Chem. Inf. Model. 51 (2011) 558-571.
41. S.-Y. Lu, Y.-J. Jiang, J. Lv, T.-X. Wu, Q.-S. Yu, W.-L. Zhu, Molecular docking and molecular dynamics simulation studies of GPR40 receptor-agonist interactions, J. Mol. Graph. Model. 28 (2010) 766-774.
42. S.-Y. Lu, Y.-J. Jiang, J.-W. Zou, H.-B. Luo, T.-X. Wu, Insights into analysis of interactions of GW9508 to wild-type and H86F and H137F GPR40: a combined QM/MM study and pharmacophore modeling, J. Mol. Graph. Model. 29 (2011) 818-825.
43. S.-Y. Lu, Y.-J. Jiang, J.-W. Zou, T.-X. Wu, Role of bridging water molecules in GSK3β-inhibitor complexes: insights fromQM/MM,MDand molecular docking studies, J. Comput. Chem. 32 (2011) 1907-1918.
44. D.A. Case, T.A. Darden, T.E. Cheatham III, C. Simmerling, J. Wang, R.E. Duke, R. Luo, K.M. Merz, D.A. Pearlman, M. Crowley, R.C. Walker, B. Zhang, S. Wang, A. Hayik, G. Roitberg, K.F. Seabra, F. Wong, X. Paesani, S. Wu, V. Brozell, H. Tsui, L. Gohlke, C. Yang, J. Tan, V. Mongan, G. Hornak, P. Cui, D.H. Beroza, C. Mathews, W.S.R. Schafmeister, P.A. Kollman, AMBER 9, University of California, San Francisco, 2006.
45. Y. Duan, C. Wu, S. Chowdhury, M.C. Lee, G. Xiong, W. Zhang, R. Yang, P. Cieplak, R. Luo, T. Lee, A point-charge force field for molecular mechanics simulations of proteins, J. Comput. Chem. 24 (2003) 1999-2012.
46. J. Wang, R.M. Wolf, J.W. Caldwell, P.A. Kollman, D.A. Case, Development and testing of a general Amber force field, J. Comput. Chem. 25 (2004) 1157-1174.
47. G. Mukherjee, N. Patra, P. Barua, B. Jayaram, A fast empirical GAFF compatible partial atomic charge assignment scheme for modeling interactions of small molecules with biomolecular targets, J. Comput. Chem. 32 (2011) 893-907.
48. M.J. Frisch, G.W. Trucks, H.B. Schlegel, G.E. Scuseria, M.A. Robb, J.R. Cheeseman, J.A. Montgomery Jr., T. Vreven, K.N. Kudin, J.C. Burant, J.M.Millam, S.S. Iyengar, J. Tomasi, V. Barone, B. Mennucci, M. Cossi, G. Scalmani, N. Rega, G.A. Petersson, H. Nakatsuji, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, M. Klene, X. Li, J.E. Knox, H.P. Hratchian, J.B. Cross, C. Adamo, J. Jaramillo, R. Gomperts, R.E. Stratmann, O. Yazyev, A.J. Austin, R. Cammi, C. Pomelli, J.W. Ochterski, P.Y. Ayala, K. Morokuma, G.A. Voth, P. Salvador, J.J. Dannenberg, V.G. Zakrzewski, S. Dapprich, A.D. Daniels, M.C. Strain, O. Farkas, D.K. Malick, A.D. Rabuck, K. Raghavachari, J.B. Foresman, J.V. Ortiz, Q. Cui, A.G. Baboul, S. Clifford, J. Cioslowski, B.B. Stefanov, G. Liu, A. Liashenko, P. Piskorz, I. Komaromi, R.L. Martin, D.J. Fox, T. Keith, M.A. Al-Laham, C.-Y. Peng, A. Nanayakkara, M. Challacombe, P.M.W. Gill, B. Johnson, W. Chen, M.-W. Wong, C. Gonzalez, J.A. Pople, Guassian 03, Gaussian, Inc., Wallingford, CT, 2003.
49. W.L. Jorgensen, J. Chandrasekhar, J.D. Madura, R.W. Impey, M.L. Klein, Comparison of single potential function for simulating liquid water, J. Chem. Phys. 79 (1983) 926-935.
50. T. Darden, D. York, L. Pedersen, Particle mesh Ewald: an Nlog(N) method for Ewald sums in large systems, J. Chem. Phys. 98 (1993) 10089-10094.
51. J.P. Ryckaert, G. Ciccotti, H.J.C. Berendsen, Numerical integration of the Cartesian equations of motion of a system with constraints: molecular dynamics of n-alkanes, J. Comput. Phys. 23 (1977) 327-341.
52. X. Wu, B.R. Brooks, Self-guided Langevin dynamics simulation method, Chem. Phys. Lett. 381 (2003) 518-521.
53. B.P. Ling, L.H. Dong, R. Zhang, Z.G. Wang, Y.J. Liu, C.B. Liu, Theoretical studies on the interaction of XIAP-BIR3 domain with bicyclic and tricyclic core monovalent Smacmimetics, J. Mol. Graph. Model. 29 (2010) 354-362.
54. Y. Yang, J. Qin, H. Liu, X. Yao, Molecular dynamics simulation free energy calculation and structure-based 3D-QSAR studies of B-RAF kinase inhibitors, J. Chem. Inf. Model. 50 (2011) 1574-1588.
55. T. Hou, J. Wang, Y. Li, W. Wang, Assessing the performance of the molecular mechanics/Poisson Boltzmann surface area and molecular mechanics/ generalized Born surface area methods. II. The accuracy of ranking poses generated from docking, J. Comput. Chem. 32 (2011) 866-877.
56. T. Hou, J. Wang, Y. Li, W. Wang, Assessing the performance of the MM/PBSA and MM/GBSA methods. 1. The accuracy of binding free energy calculations based on molecular dynamics simulations, J. Chem. Inf. Model. 51 (2011) 69-82.
57. L. Saiz-Urra, M.A. Cabrera, M. Froeyen, Exploring the conformational changes of the ATP binding site of gyrase B from Escherichia coli complexed with different established inhibitors by using molecular dynamics simulation. Protein-ligand interactions in the light of the alanine scanning and free energy decomposition methods, J. Mol. Graph. Model. 29 (2011) 726-739.
58. N.M.Micaelo, A.L. Macedo, B.J. Goodfellow, V. Felix, Tetrapyrrole binding affinity of the murine and human p22HBP heme-binding proteins, J. Mol. Graph. Model. 29 (2010) 396-405.
59. D.A. Case, T.E. Cheatham, T. Darden, H. Gohlke, R. Luo, K.M.Merz, A. Onufriev, C. Simmerling, B. Wang, R.J. Woods, The Amber biomolecular simulation program, J. Comput. Chem. 26 (2005) 1668-1688.
60. Y. Ding, Y. Mei, J.Z.H. Zhang, Quantum mechanical studies of residue-specific hydrophobic interaction in p53-MDM2 binding, J. Phys. Chem. B 112 (2008) 11396-11401.
61. L.T. Chong, Y. Duan, L. Wang, I. Massova, P.A. Kollman, Molecular dynamics and free-energy calculations applied to affinity maturation in antibody 48G7, Proc. Natl. Acad. Sci. U.S.A. 96 (1999) 14330-14335. (Pubitemid 30000650)
62. B. Kuhn, P.A. Kollman, Binding of a diverse set of ligands to avidin and streptavidin: an accurate quantitative prediction of their relative affinities by a combination of molecular mechanics and continuum solvation models, J. Med. Chem. 43 (2000) 3786-3791.
63. S. Huo, J. Wang, P. Cieplak, P.A. Kollman, I.D. Kuntz, Molecular dynamics and free energy analyses of cathepsin D-inhibitor interactions: insights into structurebased ligand design, J. Med. Chem. 45 (2002) 1412-1419. (Pubitemid 34246104)
64. I. Massova, P.A. Kollman, Computational alanine scanning to probe protein-protein interactions: a novel approach to evaluate binding free energies, J. Am. Chem. Soc. 121 (1999) 8133-8143. (Pubitemid 29444447)
65. G.W. Yu, M. Vaysburd, M.D. Allen, G. Settanni, A.R. Fersht, Structure of human MDM4 N-terminal domain bound to a single-domain antibody, J. Mol. Biol. 385 (2009) 1578-1589.
66. I.S. Moreira, P.A. Fernandes, M.J. Ramos, Protein-protein recognition: a computational mutagenesis study of the MDM2-P53 complex, Theor. Chem. Acc. 120 (2008) 533-542.
67. B. Ma, R. Nussinov, Trp/Met/Phe hot spots in protein-protein interactions: potential targets in drug design, Curr. Top. Med. Chem. 7 (2007) 999-1005. (Pubitemid 47040527)
68. L.M. Espinoza-Fonseca, J. García-Machorro, Aromatic-aromatic interactions in the formation of the MDM2-p53 complex, Biochem. Biophys. Res. Commun. 370 (2008) 547-551.
69. A.C. Wallace, R.A. Laskowski, J.M. Thornton, LIGPLOT: a program to generate schematic diagrams of protein-ligand interactions, Protein Eng. 8 (1995) 127-134.
70. K. Sakurai, C. Schubert, D. Kahne, Crystallographic analysis of an 8-mer p53 peptide analogue complexed with MDM2, J. Am. Chem. Soc. 128 (2006) 11000-11001. (Pubitemid 44300090)
71. C. Riedinger, J.M. McMonnell, Inhibitors of MDM2 and MDMX: a structural perspective, Future Med. Chem. 1 (2009) 1075-1094.