Molecular dynamics of protein kinase-inhibitor complexes: A valid structural information

Current Pharmaceutical Design

Volumn 18, Issue 20, 2012, Pages 2946-2963

  Caballero, Julio ^a   Alzate Morales, Jans H ^a  

^a UNIVERSIDAD DE TALCA   (Chile)

Author keywords

4D QSAR; Docking; Free energy calculations; Molecular dynamics; Protein kinases

Indexed keywords

PROTEIN KINASE; PROTEIN KINASE INHIBITOR;

CALCULATION; DRUG ACTIVITY; DRUG STRUCTURE; ENZYME INHIBITION; ENZYME INHIBITOR COMPLEX; ENZYME INHIBITOR INTERACTION; ENZYME PHOSPHORYLATION; ENZYME STRUCTURE; MOLECULAR DYNAMICS; PRIORITY JOURNAL; QUANTITATIVE STRUCTURE ACTIVITY RELATION; REVIEW; SIMULATION; X RAY CRYSTALLOGRAPHY;

EID: 84861751800     PISSN: 13816128     EISSN: 18734286     Source Type: Journal    
DOI: 10.2174/138161212800672705     Document Type: Review

References (121)

1. Rubin GM, Yandell MD, Wortman JR, et al. Comparative genomics of the eukaryotes. Science 2000; 287: 2204-15.
2. Cohen P. Protein kinases-the major drug targets of the twenty-first century? Nat. Rev. Drug Discov 2002; 1: 309-15.
3. Manning G, Whyte DB, Martinez R, Hunter T, Sudarsanam S. The Protein Kinase Complement of the Human Genome. Science 2002; 298: 1912-1934.
4. Porter AC, Vaillancourt RR. Tyrosine kinase receptor-activated signal transduction pathways which lead to oncogenesis. Oncogene 1998; 17: 1343-52.
5. Zhang H, Berezov A, Wang Q, et al. ErbB receptors: from oncogenes to targeted cancer therapies. J Clin Invest 2007; 117: 2051-8.
6. Williams LT. Signal transduction by the platelet-derived growth factor receptor. Science 1989; 243: 1564-70.
7. Heldin CH. Platelet-derived growth factor--an introduction. Cytokine Growth Factor Rev 2004; 15: 195-6.
8. Vu CB. Recent advances in the design and synthesis of SH2 inhibitors of Src, Grb2 and ZAP-70. Curr Med Chem 2000; 7: 1081-100.
9. Lawrence DS, Niu J. Protein kinase inhibitors: the tyrosine-specific protein kinases. Pharmacol Ther 1998; 77: 81-114.
10. Mitchell T, Showell GA. Design strategies for building drug-like chemical libraries. Curr Opin Drug Discov Devel 2001; 4: 314-8.
11. Adams JA. Kinetic and catalytic mechanisms of protein kinases. Chem Rev 2001; 101: 2271-90.
12. Zhang J, Yang PL, Gray NS. Targeting cancer with small molecule kinase inhibitors. Nat Rev Cancer 2009; 9: 28-39.
13. Tarricone C, Dhavan R, Peng J, Areces LB, Tsai LH, Musacchio A. Structure and regulation of the CDK5-p25(nck5a) complex. Mol Cell 2001; 8: 657-69.
14. Wybenga-Groot LE, Baskin B, Ong SH, Tong J, Pawson T, Sicheri F. Structural basis for autoinhibition of the Ephb2 receptor tyrosine kinase by the unphosphorylated juxtamembrane region. Cell 2001; 106: 745-757.
15. Day PJ, Cleasby A, Tickle IJ, et al. Crystal structure of human CDK4 in complex with a D-type cyclin. Proc. Natl. Acad. Sci. U.S. A 2009; 106: 4166-4170.
16. Honma T, Hayashi K, Aoyama T, et al. Structure-based generation of a new class of potent Cdk4 inhibitors: new de novo design strategy and library design. J. Med. Chem 2001; 44: 4615-4627.
17. Honma T, Yoshizumi T, Hashimoto N, et al. A novel approach for the development of selective Cdk4 inhibitors: library design based on locations of Cdk4 specific amino acid residues. J Med Chem 2001; 44: 4628-40.
18. Gibson AE, Arris CE, Bentley J, et al. Probing the ATP Ribose-Binding Domain of Cyclin-Dependent Kinases 1 and 2 with O6-Substituted Guanine Derivatives. J Med Chem 2002; 45: 3381-93.
19. Hardcastle IR, Arris CE, Bentley J, et al. N2-Substituted O6-Cyclohexylmethylguanine Derivatives: Potent Inhibitors of Cyclin-Dependent Kinases 1 and 2. J Med Chem 2004; 47: 3710-22.
20. Gellibert F, Woolven J, Fouchet MH, et al. Identification of 1,5-naphthyridine derivatives as a novel series of potent and selective TGF-beta type I receptor inhibitors. J Med Chem 2004; 47: 4494-506.
21. Harris PA, Boloor A, Cheung M, et al. Discovery of 5-[4-[(2,3-dimethyl-2H-indazol-6-yl)methylamino]-2-pyrimidinyl]amino]-2-m ethyl-benzenesulfonamide (Pazopanib), a novel and potent vascular endothelial growth factor receptor inhibitor. J Med Chem 2008; 51: 4632-40.
22. Pratt DJ, Bentley J, Jewsbury P, Boyle FT, Endicott JA, Noble ME. Dissecting the determinants of cyclin-dependent kinase 2 and cyclin-dependent kinase 4 inhibitor selectivity. J Med Chem 2006; 49: 5470-7.
23. Lu H, Schulze-Gahmen U. Toward understanding the structural basis of cyclin-dependent kinase 6 specific inhibition. J Med Chem 2006; 49: 3826-31.
24. Wyatt PG, Woodhead AJ, Berdini V, et al. Identification of N-(4-piperidinyl)-4-(2,6-dichlorobenzoylamino)-1H-pyrazole-3-carboxamide (AT7519), a novel cyclin dependent kinase inhibitor using fragment-based X-ray crystallography and structure based drug design. J. Med. Chem 2008; 51: 4986-4999.
25. Berger DM, Torres N, Dutia M, et al. Non-hinge-binding pyrazolo[1,5-a]pyrimidines as potent B-Raf kinase inhibitors. Bioorg. Med. Chem. Lett 2009; 19: 6519-6523.
26. Revesz L, Schlapbach A, Aichholz R, et al. In vivo and in vitro SAR of tetracyclic MAPKAP-K2 (MK2) inhibitors. Part I. Bioorg Med Chem Lett 2010; 20: 4715-8.
27. Oza V, Ashwell S, Brassil P, et al. Discovery of a novel class of triazolones as Checkpoint Kinase inhibitors-Hit to lead exploration. Bioorg Med Chem Lett 2010; 20: 5133-8.
28. Gopalsamy A, Ciszewski G, Hu Y, et al. Identification of pyrazolo[1,5-a]pyrimidine-3-carboxylates as B-Raf kinase inhibitors. Bioorg. Med. Chem. Lett 2009; 19: 2735-2738.
29. Tsou HR, Otteng M, Tran T, et al. 4-(Phenylaminomethylene) isoquinoline-1,3(2H,4H)-diones as potent and selective inhibitors of the cyclin-dependent kinase 4 (CDK4). J Med Chem 2008; 51: 3507-25.
30. Brana MF, Cacho M, Garcia ML, et al. Pyrazolo[3,4-c]pyridazines as novel and selective inhibitors of cyclin-dependent kinases. J. Med. Chem 2005; 48: 6843-6854.
31. Shi J, Xu G, Zhu W, et al. Design and synthesis of 1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazoles and pyrazolo[3,4-b]pyridines for Aurora-A kinase inhibitors. Bioorg. Med. Chem. Lett 2010; 20: 4273-8.
32. Li X, Wang L, Long L, Xiao J, Hu Y, Li S. Synthesis and biological evaluation of 1,2,4-trisubstituted imidazoles and 1,3,5-trisubstituted pyrazoles as inhibitors of transforming growth factor beta type 1 receptor (ALK5). Bioorg Med Chem Lett 2009; 19: 4868-72.
33. Lv PC, Li HQ, Sun J, Zhou Y, Zhu HL. Synthesis and biological evaluation of pyrazole derivatives containing thiourea skeleton as anticancer agents. Bioorg Med Chem 2010; 18: 4606-14.
34. Conchon E, Anizon F, Aboab B, et al. Synthesis, checkpoint kinase 1 inhibitory properties and in vitro antiproliferative activities of new pyrrolocarbazoles. Bioorg. Med. Chem 2008; 16: 4419-4430.
35. Payne MC, Teter MP, Allan DC, Arias TA, Joannopoulos JD. Iterative minimization techniques for ab initio total-energy calculations: molecular dynamics and conjugate gradients. Rev Modern Phys 1992; 64: 1045-97.
36. Cornell WD, Cieplak P, Bayly CI, et al. A second generation force field for the simulation of proteins, nucleic acids, and organic molecules. J Am Chem Soc 1995; 117: 5179-97.
37. Brooks BR, Bruccoleri RE, Olafson BD, States DJ, Swaminathan S, Karplus M. CHARMM: A program for macromolecular energy, minimization, and dynamics calculations. J Comput Chem 1983; 4: 187-217.
38. Schuler LD, Daura X, van Gunsteren WF. An improved GROMOS96 force field for aliphatic hydrocarbons in the condensed phase. J Comput Chem 2001; 22: 1205-1218.
39. Jorgensen WL, Maxwell DS, Tirado-Rives J. Development and Testing of the OPLS All-Atom Force Field on Conformational Energetics and Properties of Organic Liquids. J. Am. Chem. Soc 1996; 118: 11225-36.
40. Cheatham TE, III, Miller JL, Fox T, Darden TA, Kollman PA. Molecular dynamics simulations on solvated biomolecular systems: The particle mesh Ewald method leads to stable trajectories of DNA, RNA, and proteins. J Am Chem Soc 1995; 117: 4193-4.
41. Ryckaert JP, Ciccotti G, Berendsen HJC. Numerical integration of the cartesian equations of motion of a system with constraints: molecular dynamics of n-alkanes. J Comput Phys 1977; 23: 327-41.
42. Nose S. A unified formulation of the constant temperature molecular-dynamics methods. J Chem Phys 1984; 81: 511-9.
43. Hoover WG. Canonical dynamics: Equilibrium phase-space distributions. Phys. Rev. A 1985; 31: 1695-7.
44. Berendsen HJC, Postma JPM, van Gunsteren WF, DiNola A, Haak JR. Molecular dynamics with coupling to an external bath. J Chem Phys 1984; 81: 3684-90.
45. van Gunsteren WF, Berendsen HJC. Computer simulation of molecular dynamics: methodology, applications, and perspectives in chemistry. Angew Chem Int Ed 1990; 29: 992-1023.
46. van Aalten DM, Bywater R, Findlay JB, Hendlich M, Hooft RW, Vriend G. PRODRG, a program for generating molecular topologies and unique molecular descriptors from coordinates of small molecules. J Comput-Aided Mol Des 1996; 10: 255-62.
47. Wang J, Wang W, Kollman PA, Case DA. ANTECHAMBER: an accessory software package for molecular mechanical calculations. Abstr Pap Am Chem Soc 2001; 222: U403.
48. Zoete V, Cuendet MA, Grosdidier A, Michielin O. SwissParam: a fast force field generation tool for small organic molecules. J Comput Chem 2011; 32: 2359-68.
49. Vanommeslaeghe K, Hatcher E, Acharya C, et al. CHARMM general force field: A force field for drug-like molecules compatible with the CHARMM all-atom additive biological force fields. J Comput Chem 2010; 31: 671-90.
50. PrimeX, version 1.6 2009. Schrödinger, LLC: New York, NY.
51. Withers IM, Mazanetz MP, Wang H, Fischer PM, Laughton CA. Active site pressurization: a new tool for structure-guided drug design and other studies of protein flexibility. J Chem Inf Model 2008; 48: 1448-54.
52. Young T, Abel R, Kim B, Berne BJ, Friesner RA. Motifs for molecular recognition exploiting hydrophobic enclosure in proteinligand binding. Proc Natl Acad Sci USA 2007; 104: 808-13.
53. Robinson DD, Sherman W, Farid R. Understanding kinase selectivity through energetic analysis of binding site waters. Chem Med Chem 2010; 5: 618-27.
54. Meshkat S, Klon AE, Zou J, Wiseman JS, Konteatis Z. Transplantinsert-constrain-relax-assemble (TICRA): protein-ligand complex structure modeling and application to kinases. J Chem Inf Model 2011; 51: 52-60.
55. Kokh DB, Wade RC, Wenzel W. Receptor flexibility in smallmolecule docking calculations. WIREs Comput Mol Sci 2011; 1: 298-314.
56. Talele TT, McLaughlin ML. Molecular docking/dynamics studies of Aurora A kinase inhibitors. J Mol Graph Model 2008; 26: 1213-22.
57. Wang F, Ma Z, Li Y, et al. Development of in silico models for pyrazoles and pyrimidine derivatives as cyclin-dependent kinase 2 inhibitors. J Mol Graph Model 2011; 30: 67-81.
58. Park H, Yeom MS, 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 2004; 5: 1662-72.
59. Lin FY, Tseng YJ. Structure-based fragment hopping for lead optimization using predocked fragment database. J Chem Inf Model 2011; 51: 1703-15.
60. Golub AG, Bdzhola VG, Kyshenia YV, et al. Structure-based discovery of novel flavonol inhibitors of human protein kinase CK2. Mol Cell Biochem 2011; 356: 107-15.
61. Tanneeru K, Guruprasad L. Ligand-based 3-D pharmacophore generation and molecular docking of mTOR kinase inhibitors. J Mol Model 2011 doi: 10.1007/s00894-011-1184-3.
62. Alzate-Morales JH, Caballero J, Vergara-Jaque A, González-Nilo FD. Insights into the structural basis of N2 and O6 substituted guanine derivatives as cyclin-dependent kinase 2 (CDK2) inhibitors: prediction of the binding modes and potency of the inhibitors by docking and ONIOM calculations. J Chem Inf Model 2009; 49: 886-99.
63. Alzate-Morales J, Caballero J. Computational Study of the Interactions between Guanine Derivatives and Cyclin-Dependent Kinase 2 (CDK2) by CoMFA and QM/MM. J Chem Inf Model 2010; 50: 110-22.
64. Alzate-Morales JH, Vergara-Jaque A, Caballero J. Computational Study on the Interaction of N1 Substituted Pyrazole Derivatives with B-Raf Kinase: An Unusual Water Wire Hydrogen-Bond Network and Novel Interactions at the Entrance of the Active Site. J Chem Inf Model 2010; 50: 1101-12.
65. Caballero J, Alzate-Morales JH, Vergara-Jaque A. Investigation of the differences in activity between hydroxycycloalkyl N1 substituted pyrazole derivatives as inhibitors of B-Raf kinase by using docking, molecular dynamics, QM/MM, and fragment-based de novo design: study of binding mode of diastereomer compounds. J Chem Inf Model 2011; 51: 2920-31.
66. Huo S, Wang J, Cieplak P, Kollman PA, Kuntz ID. Molecular dynamics and free energy analyses of cathepsin D-inhibitor interactions: insight into structure-based ligand design. J Med Chem 2002; 45: 1412-9.
67. Kollman PA, Massova I, Reyes C, et al. Calculating structures and free energies of complex molecules: combining molecular mechanics and continuum models. Acc Chem Res 2000; 33: 889-97.
68. Straatsma TP, McCammon JA. Computational alchemy. Annu Rev Phys Chem 1992; 43: 407-35.
69. Pearlman DA, Charifson PS. Are free energy calculations useful in practice? A comparison with rapid scoring functions for the p38 MAP kinase protein system. J Med Chem 2001; 44: 3417-23.
70. Myrianthopoulos V, Magiatis P, Ferandin Y, Skaltsounis AL, Meijer L, Mikros E. An integrated computational approach to the phenomenon of potent and selective inhibition of aurora kinases B and C by a series of 7-substituted indirubins. J Med Chem 2007; 50: 4027-37.
71. Valeyev NV, Aleksandrov A. An atomistic model for simulations of nilotinib and nilotinib/kinase binding. Theor Chem Acc 2011; 129: 747-56.
72. Aqvist J, Medina C, Samuelsson JE. A new method for predicting binding affinity in computer-aided drug design. Protein Eng 1994; 7: 385-91.
73. Swanson JM, Henchman RH, McCammon JA. Revisiting free energy calculations: a theoretical connection to MM/PBSA and direct calculation of the association free energy. Biophys J 2004; 86: 67-74.
74. Aqvist J, Luzhkov VB, Brandsdal BO. Ligand binding affinities from MD simulations. Acc Chem Res 2002; 35: 358-65.
75. Srinivasan J, Cheatham TE, Cieplak P, Kollman PA, Case DA. Continuum solvent studies of the stability of DNA, RNA, and phosphoramidate-DNA helices. J Am Chem Soc 1998; 120: 9401-9.
76. Suarez E, Diaz N, Suarez D. Entropy Calculations of Single Molecules by Combining the Rigid-Rotor and Harmonic-Oscillator Approximations with Conformational Entropy Estimations from Molecular Dynamics Simulations. J Chem Theory Comput 2011; 7: 2638-53.
77. Armen RS, Chen J, Brooks CL, 3rd. An Evaluation of Explicit Receptor Flexibility in Molecular Docking Using Molecular Dynamics and Torsion Angle Molecular Dynamics. J Chem Theory Comput 2009; 5: 2909-13.
78. Abdulhameed MD, Hamza A, Zhan CG. Microscopic modes and free energies of 3-phosphoinositide-dependent kinase-1 (PDK1) binding with celecoxib and other inhibitors. J. Phys. Chem. B 2006; 110: 26365-74.
79. Wan S, Coveney PV. Rapid and accurate ranking of binding affinities of epidermal growth factor receptor sequences with selected lung cancer drugs. J R Soc Interface 2011; 8: 1114-27.
80. Muzzioli E, Del Rio A, Rastelli G. Assessing protein kinase selectivity with molecular dynamics and mm-pbsa binding free energy calculations. Chem. Biol. Drug Des 2011; 78: 252-9.
81. Chen Q, Cui W, Cheng Y, Zhang F, Ji M. Studying the mechanism that enables paullones to selectively inhibit glycogen synthase kinase 3 rather than cyclin-dependent kinase 5 by molecular dynamics simulations and free-energy calculations. J Mol Model 2011; 17: 795-803.
82. Jiang Y, Zou J, Gui C. Study of a ligand complexed with Cdk2/Cdk4 by computer simulation. J Mol Model 2005; 11: 509-15.
83. Zhang B, Tan VB, Lim KM, Tay TE. Molecular dynamics simulations on the inhibition of cyclin-dependent kinases 2 and 5 in the presence of activators. J. Comput.-Aided Mol. Des 2006; 20: 395-404.
84. Zhang B, Tan VB, Lim KM, Tay TE, Zhuang S. Study of the inhibition of cyclin-dependent kinases with roscovitine and indirubin-3'-oxime from molecular dynamics simulations. J Mol Model 2007; 13: 79-89.
85. Tan VB, Zhang B, Lim KM, Tay TE. Explaining the inhibition of cyclin-dependent kinase 5 by peptides derived from p25 with molecular dynamics simulations and MM-PBSA. J Mol Model 2010; 16: 1-8.
86. Zhang B, Corbel C, Gueritte F, Couturier C, Bach S, Tan VB. An in silico approach for the discovery of CDK5/p25 interaction inhibitors. Biotechnol. J 2011; 6: 871-81.
87. Kortemme T, Kim DE, Baker D. Computational alanine scanning of protein-protein interfaces. Sci STKE 2004; 2004: pl2.
88. Pearlman DA. Evaluating the molecular mechanics poissonboltzmann surface area free energy method using a congeneric series of ligands to p38 MAP kinase. J Med Chem 2005; 48: 7796-807.
89. Dubey KD, Ojha RP. Conformational flexibility, binding energy, role of salt bridge and alanine-mutagenesis for c-Abl kinase complex. J Mol Model 2011 doi: 10.1007/s00894-011-1199-9.
90. Li Y, Zhang J, He D, Liang Q, Wang Y. Characterization of molecular recognition of Phosphoinositide-3-kinase alpha inhibitor through molecular dynamics simulation. J Mol Model 2011 doi: 10.1007/s00894-011-1211-4.
91. Jena NR. Binding of BIS like and other ligands with the GSK-3beta kinase: a combined docking and MM-PBSA study. J Mol Model 2012; 18: 631-44.
92. Del Rio A, Sgobba M, Parenti MD, et al. A computational workflow for the design of irreversible inhibitors of protein kinases. J Comput-Aided Mol Des 2010; 24: 183-94.
93. Cheng Y, Cui W, Chen Q, Tung CH, Ji M, Zhang F. The molecular mechanism studies of chirality effect of PHA-739358 on Aurora kinase A by molecular dynamics simulation and free energy calculations. J Comput-Aided Mol Des 2011; 25: 171-80.
94. Wichapong K, Lawson M, Pianwanit S, Kokpol S, Sippl W. Postprocessing of protein-ligand docking poses using linear response MM-PB/SA: application to Wee1 kinase inhibitors. J Chem Inf Model 2010; 50: 1574-88.
95. Page CS, Bates PA. Can MM-PBSA calculations predict the specificities of protein kinase inhibitors? J Comput Chem 2006; 27: 1990-2007.
96. Yang T, Wu JC, Yan C, et al. Virtual screening using molecular simulations. Proteins 2011; 79: 1940-51.
97. Muñoz C, Adasme F, Alzate-Morales JH, Vergara-Jaque A, Kniess T, Caballero J. Study of differences in the VEGFR2 inhibitory activities between semaxanib and SU5205 using 3D-QSAR, docking, and molecular dynamics simulations. J Mol Graph Model 2012; 32: 39-48.
98. Lee MS, Olson MA. Calculation of absolute protein-ligand binding affinity using path and endpoint approaches. Biophys J 2006; 90: 864-77.
99. Torrie GM, Valleau JP. Nonphysical sampling distributions in Monte Carlo free-energy estimation: umbrella sampling. J Comput Phys 1977; 23: 187-99.
100. Park S, Khalili-Araghi F, Tajkhorshid E, Schulten K. Free energy calculation from steered molecular dynamics simulations using Jarzynski's equality. J Chem Phys 2003; 119: 3559
101. Laio A, Parrinello M. Escaping free-energy minima. Proc Natl Acad Sci USA 2002; 99: 12562-6.
102. Iannuzzi M, Laio A, Parrinello M. Efficient exploration of reactive potential energy surfaces using Car-Parrinello molecular dynamics. Phys Rev Lett 2003; 90: 238302.
103. Darve E, Rodriguez-Gomez D, Pohorille A. Adaptive biasing force method for scalar and vector free energy calculations. J Chem Phys 2008; 128: 144120.
104. Doudou S, Sharma R, Henchman RH, Sheppard DW, Burton NA. Inhibitors of PIM-1 kinase: a computational analysis of the binding free energies of a range of imidazo [1,2-b] pyridazines. J Chem Inf Model 2010; 50: 368-79.
105. Caballero J, Fernández M, Saavedra M, González-Nilo FD. 2D Autocorrelation, CoMFA, and CoMSIA modeling of protein tyrosine kinases' inhibition by substituted pyrido[2,3-d]pyrimidine derivatives. Bioorg Med Chem 2008; 16: 810-21.
106. Caballero J, Fernández M, González-Nilo FD. Structural requirements of pyrido[2,3-d]pyrimidin-7-one as CDK4/D inhibitors: 2D autocorrelation, CoMFA and CoMSIA analyses. Bioorg Med Chem 2008; 16: 6103-15.
107. Fernandez M, Tundidor-Camba A, Caballero J. Modeling of cyclin-dependent kinase inhibition by 1H-pyrazolo[3,4-d]pyrimidine derivatives using artificial neural network ensembles. J Chem Inf Model 2005; 45: 1884-95.
108. González M, Caballero J, Helguera A, Garriga M, González G, Fernández M. 2D Autocorrelation Modelling of the Inhibitory Activity of Cytokinin-Derived Cyclin-Dependent Kinase Inhibitors. Bull Math Biol 2006; 68: 735-51.
109. Caballero J, Quiliano M, Alzate-Morales JH, Zimic M, Deharo E. Docking and quantitative structure-activity relationship studies for 3-fluoro-4-(pyrrolo[2,1-f][1,2,4]triazin-4-yloxy)aniline, 3-fluoro-4-(1H-pyrrolo[2,3-b]pyridin-4-yloxy)aniline, and 4-(4-amino-2-fluorophenoxy)-2-pyridinylamine derivatives as c-Met kinase inhibitors. J Comput-Aided Mol Des 2011; 25: 349-69.
110. Hopfinger AJ, Wang S, Tokarski JS, et al. Construction of 3DQSAR Models Using the 4D-QSAR Analysis Formalism. J Am Chem Soc 1997; 119: 10509-24.
111. Venkatarangan P, Hopfinger AJ. Prediction of ligand-receptor binding free energy by 4D-QSAR analysis: application to a set of glucose analogue inhibitors of glycogen phosphorylase. J Chem Inf Comput Sci 1999; 39: 1141-50.
112. Cramer RD, Patterson DE, Bunce JD. Comparative molecular field analysis (CoMFA). 1. Effect of shape on binding of steroids to carrier proteins. J Am Chem Soc 1988; 110: 5959-67.
113. Romeiro NC, Albuquerque MG, de Alencastro RB, Ravi M, Hopfinger AJ. Construction of 4D-QSAR models for use in the design of novel p38-MAPK inhibitors. J Comput-Aided Mol Des 2005; 19: 385-400.
114. Martins JP, Barbosa EG, Pasqualoto KF, Ferreira MM. LQTAQSAR: a new 4D-QSAR methodology. J Chem Inf Model 2009; 49: 1428-36.
115. Lindahl E, Hess B, van der Spoel D. GROMACS 3.0: a package for molecular simulation and trajectory analysis. J Mol Model 2001; 7: 306-17.
116. Pan D, Tseng Y, Hopfinger AJ. Quantitative structure-based design: formalism and application of receptor-dependent RD-4D QSAR analysis to a set of glucose analogue inhibitors of glycogen phosphorylase. J Chem Inf Comput Sci 2003; 43: 1591-607.
117. Wang J, Verkhivker GM. Energy landscape theory, funnels, specificity, and optimal criterion of biomolecular binding. Phys Rev Lett 2003; 90: 188101.
118. Zwanzig R, Szabo A, Bagchi B. Levinthal's paradox. Proc Natl Acad Sci USA 1992; 89: 20-2.
119. Levinson NM, Kuchment O, Shen K, et al. A Src-like inactive conformation in the abl tyrosine kinase domain. PLoS Biol 2006; 4: e144.
120. Shan Y, Seeliger MA, Eastwood MP, et al. A conserved protonation-dependent switch controls drug binding in the Abl kinase. Proc Natl Acad Sci USA 2009; 106: 139-44.
121. Shan Y, Kim ET, Eastwood MP, Dror RO, Seeliger MA, Shaw DE. How does a drug molecule find its target binding site? J Am Chem Soc 2011; 133: 9181-3.