Molecular Dynamics Simulations and Structural Network Analysis of c-Abl and c-Src Kinase Core Proteins: Capturing Allosteric Mechanisms and Communication Pathways from Residue Centrality

Journal of Chemical Information and Modeling

Volumn 55, Issue 8, 2015, Pages 1645-1662

  Tse, Amanda ^a   Verkhivker, Gennady M ^a  

^a CHAPMAN UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMINO ACIDS; CATALYST ACTIVITY; CHEMICAL ACTIVATION; MOLECULAR DYNAMICS;

COMMUNICATION PATHWAYS; COMPUTATIONAL INVESTIGATION; CRYSTALLOGRAPHIC STUDIES; DIFFERENTIAL SENSITIVITY; MOLECULAR CHARACTERIZATION; MOLECULAR DYNAMICS SIMULATIONS; STRUCTURAL NETWORK ANALYSIS; STRUCTURAL ORGANIZATION;

ENZYMES;

ABELSON KINASE; CSK TYROSINE-PROTEIN KINASE; PROTEIN TYROSINE KINASE;

ALLOSTERISM; CHEMISTRY; HUMAN; METABOLISM; MOLECULAR DYNAMICS; PROTEIN CONFORMATION; PROTEIN PROTEIN INTERACTION; SIGNAL TRANSDUCTION; SRC HOMOLOGY DOMAIN;

ALLOSTERIC REGULATION; HUMANS; MOLECULAR DYNAMICS SIMULATION; PROTEIN CONFORMATION; PROTEIN INTERACTION MAPS; PROTO-ONCOGENE PROTEINS C-ABL; SIGNAL TRANSDUCTION; SRC HOMOLOGY DOMAINS; SRC-FAMILY KINASES;

EID: 84940176602     PISSN: 15499596     EISSN: 1549960X     Source Type: Journal    
DOI: 10.1021/acs.jcim.5b00240     Document Type: Article

References (106)

1. Nolen, B.; Taylor, S.; Ghosh, G. Regulation of Protein Kinases; Controlling Activity Through Activation Segment Conformation Mol. Cell 2004, 15, 661-675 10.1016/j.molcel.2004.08.024
2. Noble, M. E.; Endicott, J. A.; Johnson, L. N. Protein Kinase Inhibitors: Insights into Drug Design from Structure Science 2004, 303, 1800-1805 10.1126/science.1095920
3. Huse, M.; Kuriyan, J. The conformational Plasticity of Protein Kinases Cell 2002, 109, 275-282 10.1016/S0092-8674(02)00741-9
4. Taylor, S. S.; Kornev, A. P. Protein Kinases: Evolution of Dynamic Regulatory Proteins Trends Biochem. Sci. 2011, 36, 65-77 10.1016/j.tibs.2010.09.006
5. Endicott, J. A.; Noble, M. E.; Johnson, L. N. The Structural Basis for Control of Eukaryotic Protein Kinases Annu. Rev. Biochem. 2012, 81, 587-613 10.1146/annurev-biochem-052410-090317
6. Taylor, S. S.; Keshwani, M. M.; Steichen, J. M.; Kornev, A. P. Evolution of the Eukaryotic Protein Kinases as Dynamic Molecular Switches Philos. Trans. R. Soc., B 2012, 367, 2517-2528 10.1098/rstb.2012.0054
7. Taylor, S. S.; Ilouz, R.; Zhang, P.; Kornev, A. P. Assembly of Allosteric Macromolecular Switches: Lessons from PKA Nat. Rev. Mol. Cell Biol. 2012, 13, 646-658 10.1038/nrm3432
8. Artim, S. C.; Mendrola, J. M.; Lemmon, M. A. Assessing the Range of Kinase Autoinhibition Mechanisms in the Insulin Receptor Family Biochem. J. 2012, 448, 213-220 10.1042/BJ20121365
9. Oruganty, K.; Kannan, N. Design Principles Underpinning the Regulatory Diversity of Protein Kinases Philos. Trans. R. Soc., B 2012, 367, 2529-2539 10.1098/rstb.2012.0015
10. Oruganty, K.; Kannan, N. Evolutionary Variation and Adaptation in a Conserved Protein Kinase Allosteric Network: Implications for Inhibitor Design Biochim. Biophys. Acta, Proteins Proteomics 2013, 1834, 1322-13229 10.1016/j.bbapap.2013.02.040
11. Meharena, H. S.; Chang, P.; Keshwani, M. M.; Oruganty, K.; Nene, A. K.; Kannan, N.; Taylor, S. S.; Kornev, A. P. Deciphering the Structural Basis of Eukaryotic Protein Kinase Regulation PLoS Biol. 2013, 11, e1001680 10.1371/journal.pbio.1001680
12. Pluk, H.; Dorey, K.; Superti-Furga, G. Autoinhibition of c-Abl Cell 2002, 108, 247-259 10.1016/S0092-8674(02)00623-2
13. Hantschel, O.; Nagar, B.; Guettler, S.; Kretzschmar, J.; Dorey, K.; Kuriyan, J.; Superti-Furga, G. A Myristoyl/phosphotyrosine Switch Regulates c-Abl Cell 2003, 112, 845-857 10.1016/S0092-8674(03)00191-0
14. Hantschel, O.; Superti-Furga, G. Regulation of the c-Abl and Bcr-Abl Tyrosine Kinases Nat. Rev. Mol. Cell Biol. 2004, 5, 33-44 10.1038/nrm1280
15. Boggon, T. J.; Eck, M. J. Structure and Regulation of Src Family Kinases Oncogene 2004, 23, 7918-7927 10.1038/sj.onc.1208081
16. Roskoski, R., Jr. Src Protein-Tyrosine Kinase Structure and Regulation Biochem. Biophys. Res. Commun. 2004, 324, 1155-1164 10.1016/j.bbrc.2004.09.171
17. Engen, J. R.; Wales, T. E.; Hochrein, J. M.; Meyn, M. A.; Banu Ozkan, S.; Bahar, I.; Smithgall, T. E. Structure and Dynamic Regulation of Src-Family Kinases Cell. Mol. Life Sci. 2008, 65, 3058-3073 10.1007/s00018-008-8122-2
18. Xu, W.; Harrison, S. C.; Eck, M. J. Three-Dimensional Structure of the Tyrosine Kinase c-Src Nature 1997, 385, 595-601 10.1038/385595a0
19. Xu, W.; Doshi, A.; Lei, M.; Eck, M. J.; Harrison, S. C. Crystal Structures of c-Src Reveal Features of Its Autoinhibitory Mechanism Mol. Cell 1999, 3, 629-638 10.1016/S1097-2765(00)80356-1
20. Cowan-Jacob, S. W.; Fendrich, G.; Manley, P. W.; Jahnke, W.; Fabbro, D.; Liebetanz, J.; Meyer, T. The Crystal Structure of a c-Src Complex in an Active Conformation Suggests Possible Steps in c-Src Activation Structure 2005, 13, 861-871 10.1016/j.str.2005.03.012
21. Nagar, B.; Hantschel, O.; Young, M. A.; Scheffzek, K.; Veach, D.; Bornmann, W.; Clarkson, B.; Superti-Furga, G.; Kuriyan, J. Structural Basis for the Autoinhibition of c-Abl Tyrosine Kinase Cell 2003, 112, 859-871 10.1016/S0092-8674(03)00194-6
22. Nagar, B.; Hantschel, O.; Seeliger, M.; Davies, J. M.; Weis, W. I.; Superti-Furga, G.; Kuriyan, J. Organization of the SH3-SH2 Unit in Active and Inactive Forms of the c-Abl Tyrosine Kinase Mol. Cell 2006, 21, 787-798 10.1016/j.molcel.2006.01.035
23. Smith, K. M.; Yacobi, R.; Van Etten, R. A. Autoinhibition of Bcr-Abl through Its SH3 Domain Mol. Cell 2003, 12, 27-37 10.1016/S1097-2765(03)00274-0
24. Filippakopoulos, P.; Kofler, M.; Hantschel, O.; Gish, G. D.; Grebien, F.; Salah, E.; Neudecker, P.; Kay, L. E.; Turk, B. E.; Superti-Furga, G.; Pawson, T.; Knapp, S. Structural Coupling of SH2-Kinase Domains Links Fes and Abl Substrate Recognition and Kinase Activation Cell 2008, 134, 793-803 10.1016/j.cell.2008.07.047
25. Hantschel, O. Structure, Regulation, Signaling, and Targeting of Abl Kinases in Cancer Genes Cancer 2012, 3, 436-446 10.1177/1947601912458584
26. Panjarian, S.; Iacob, R. E.; Chen, S.; Engen, J. R.; Smithgall, T. E. Structure and Dynamic Regulation of Abl Kinases J. Biol. Chem. 2013, 288, 5443-5450 10.1074/jbc.R112.438382
27. Reddy, E. P.; Aggarwal, A. K. The Ins and Outs of Bcr-Abl Inhibition Genes Cancer 2012, 3, 447-454 10.1177/1947601912462126
28. Chen, S.; Brier, S.; Smithgall, T. E.; Engen, J. R. The Abl SH2-Kinase Linker Naturally Adopts a Conformation Competent for SH3 Domain Binding Protein Sci. 2007, 16, 572-581 10.1110/ps.062631007
29. Hochrein, J. M.; Lerner, E. C.; Schiavone, A. P.; Smithgall, T. E.; Engen, J. R. An Examination of Dynamics Crosstalk between SH2 and SH3 Domains by Hydrogen/Deuterium Exchange and Mass Spectrometry Protein Sci. 2006, 15, 65-73 10.1110/ps.051782206
30. Panjarian, S.; Iacob, R. E.; Chen, S.; Wales, T. E.; Engen, J. R.; Smithgall, T. E. Enhanced SH3/Linker Interaction Overcomes Abl Kinase Activation by Gatekeeper and Myristic Acid Binding Pocket Mutations and Increases Sensitivity to Small Molecule Inhibitors J. Biol. Chem. 2013, 288, 6116-6129 10.1074/jbc.M112.431312
31. Chen, S.; Dumitrescu, T. P.; Smithgall, T. E.; Engen, J. R. Abl N-terminal Cap Stabilization of SH3 Domain Dynamics Biochemistry 2008, 47, 5795-5803 10.1021/bi800446b
32. Barila, D.; Superti-Furga, G. An intramolecular SH3-Domain Interaction Regulates c-Abl Activity Nat. Genet. 1998, 18, 280-282 10.1038/ng0398-280
33. Brasher, B. B.; Van Etten, R. A. c-Abl Has High Intrinsic Tyrosine Kinase Activity That Is Stimulated by Mutation of the Src Homology 3 Domain and by Autophosphorylation at Two Distinct Regulatory Tyrosines J. Biol. Chem. 2000, 275, 35631-35637 10.1074/jbc.M005401200
34. Brasher, B. B.; Roumiantsev, S.; Van Etten, R. A. Mutational Analysis of the Regulatory Function of the c-Abl Src Homology 3 Domain Oncogene 2001, 20, 7744-7752 10.1038/sj.onc.1204978
35. Chen, S.; O'Reilly, L. P.; Smithgall, T. E.; Engen, J. R. Tyrosine Phosphorylation in the SH3 Domain Disrupts Negative Regulatory Interactions within the c-Abl Kinase Core J. Mol. Biol. 2008, 383, 414-423 10.1016/j.jmb.2008.08.040
36. Meyn, M. A.; Wilson, M. B.; Abdi, F. A.; Fahey, N.; Schiavone, A. P.; Wu, J.; Hochrein, J. M.; Engen, J. R.; Smithgall, T. E. Src Family Kinases Phosphorylate the Bcr-Abl SH3-SH2 Region and Modulate Bcr-Abl Transforming Activity J. Biol. Chem. 2006, 281, 30907-30916 10.1074/jbc.M605902200
37. Pene-Dumitrescu, T.; Peterson, L. F.; Donato, N. J.; Smithgall, T. E. An Inhibitor-Resistant Mutant of Hck Protects CML Cells Against the Antiproliferative and Apoptotic Effects of the Broad-Spectrum Src Family Kinase Inhibitor A-419259 Oncogene 2008, 27, 7055-7069 10.1038/onc.2008.330
38. Schindler, T.; Bornmann, W.; Pellicena, P.; Miller, W. T.; Clarkson, B.; Kuriyan, J. Structural Mechanism for STI-571 Inhibition of Abelson Tyrosine Kinase Science 2000, 289, 1938-1942 10.1126/science.289.5486.1938
39. Nagar, B.; Bornmann, W. G.; Pellicena, P.; Schindler, T.; Veach, D. R.; Miller, W. T.; Clarkson, B.; Kuriyan, J. Crystal Structures of the Kinase Domain of c-Abl in Complex with the Small Molecule Inhibitors PD173955 and Imatinib (STI-571) Cancer Res. 2002, 62, 4236-4243
40. Levinson, N. M.; Kuchment, O.; Shen, K.; Young, M. A.; Koldobskiy, M.; Karplus, M.; Cole, P. A.; Kuriyan, J. A Src-Like Inactive Conformation in the Abl Tyrosine Kinase Domain PLoS Biol. 2006, 4, e144 10.1371/journal.pbio.0040144
41. Tokarski, J. S.; Newitt, J. A.; Chang, C. Y.; Cheng, J. D.; Wittekind, M.; Kiefer, S. E.; Kish, K.; Lee, F. Y.; Borzillerri, R.; Lombardo, L. J.; Xie, D.; Zhang, Y.; Klei, H. E. The Structure of Dasatinib (BMS-354825) Bound to Activated ABL Kinase Domain Elucidates Its Inhibitory Activity against Imatinib-Resistant ABL Mutants Cancer Res. 2006, 66, 5790-5797 10.1158/0008-5472.CAN-05-4187
42. Dorey, K.; Engen, J. R.; Kretzschmar, J.; Wilm, M.; Neubauer, G.; Schindler, T.; Superti-Furga, G. Phosphorylation and Structure-Based Functional Studies Reveal a Positive and a Negative Role for the Activation Loop of the c-Abl Tyrosine Kinase Oncogene 2001, 20, 8075-8084 10.1038/sj.onc.1205017
43. Grebien, F.; Hantschel, O.; Wojcik, J.; Kaupe, I.; Kovacic, B.; Wyrzucki, A. M.; Gish, G. D.; Cerny-Reiterer, S.; Koide, A.; Beug, H.; Pawson, T.; Valent, P.; Koide, S.; Superti-Furga, G. Targeting the SH2-Kinase Interface in Bcr-Abl Inhibits Leukemogenesis Cell 2011, 147, 306-319 10.1016/j.cell.2011.08.046
44. Lamontanara, A. J.; Georgeon, S.; Tria, G.; Svergun, D. I.; Hantschel, O. The SH2 domain of Abl kinases Regulates Kinase Autophosphorylation by Controlling Activation Loop Accessibility Nat. Commun. 2014, 5, 5470 10.1038/ncomms6470
45. Lorenz, S. G.; Deng, P.; Hantschel, O.; Superti-Furga, G.; Kuriyan, J. Crystal Structure of an SH2-kinase Construct of c-Abl and Effect of the SH2 Domain on Kinase Activity Biochem. J. 2015, 468, 283-291 10.1042/BJ20141492
46. Skora, L.; Mestan, J.; Fabbro, D.; Jahnke, W.; Grzesiek, S. NMR Reveals the Allosteric Opening and Closing of Abelson Tyrosine Kinase by ATP-Site and Myristoyl Pocket Inhibitors Proc. Natl. Acad. Sci. U. S. A. 2013, 110, E4437-E4445 10.1073/pnas.1314712110
47. Lamontanara, A. J.; Gencer, E. B.; Kuzyk, O.; Hantschel, O. Mechanisms of Resistance to Bcr-Abl and Other Kinase Inhibitors Biochim. Biophys. Acta, Proteins Proteomics 2013, 1834, 1449-1459 10.1016/j.bbapap.2012.12.009
48. Sherbenou, D. W.; Hantschel, O.; Kaupe, I.; Willis, S.; Bumm, T.; Turaga, L. P.; Lange, T.; Dao, K. H.; Press, R. D.; Druker, B. J.; Superti-Furga, G.; Deininger, M. W. BCR-ABL SH3-SH2 Domain Mutations in Chronic Myeloid Leukemia Patients on Imatinib Blood 2010, 116, 3278-3285 10.1182/blood-2008-10-183665
49. Seeliger, M. A.; Nagar, B.; Frank, F.; Cao, X.; Henderson, M. N.; Kuriyan, J. C-Src Binds to the Cancer Drug Imatinib with an Inactive Abl/c-Kit Conformation and a Distributed Thermodynamic Penalty Structure 2007, 15, 299-311 10.1016/j.str.2007.01.015
50. Seeliger, M. A.; Ranjitkar, P.; Kasap, C.; Shan, Y.; Shaw, D. E.; Shah, N. P.; Kuriyan, J.; Maly, D. J. Equally Potent Inhibition of c-Src and Abl by Compounds That Recognize Inactive Kinase Conformations Cancer Res. 2009, 69, 2384-2392 10.1158/0008-5472.CAN-08-3953
51. Aleksandrov, A.; Simonson, T. A Molecular Mechanics Model for Imatinib and Imatinib:Kinase Binding J. Comput. Chem. 2010, 31, 1550-1560 10.1002/jcc.21442
52. Aleksandrov, A.; Simonson, T. Molecular Dynamics Simulations Show That Conformational Selection Governs the Binding Preferences of Imatinib for Several Tyrosine Kinases J. Biol. Chem. 2010, 285, 13807-13815 10.1074/jbc.M110.109660
53. Lovera, S.; Sutto, L.; Boubeva, R.; Scapozza, L.; Dölker, N.; Gervasio, F. L. The Different Flexibility of c-Src and c-Abl Kinases Regulates the Accessibility of a Druggable Inactive Conformation J. Am. Chem. Soc. 2012, 134, 2496-2499 10.1021/ja210751t
54. Lin, Y. L.; Meng, Y.; Jiang, W.; Roux, B. Explaining Why Gleevec is a Specific and Potent Inhibitor of Abl Kinase Proc. Natl. Acad. Sci. U. S. A. 2013, 110, 1664-1669 10.1073/pnas.1214330110
55. Lin, Y. L.; Roux, B. Computational Analysis of the Binding Specificity of Gleevec to Abl, c-Kit, Lck, and c-Src Tyrosine Kinases J. Am. Chem. Soc. 2013, 135, 14741-14753 10.1021/ja405939x
56. Lin, Y. L.; Meng, Y.; Huang, L.; Roux, B. Computational Study of Gleevec and G6G Reveals Molecular Determinants of Kinase Inhibitor Selectivity J. Am. Chem. Soc. 2014, 136, 14753-14762 10.1021/ja504146x
57. Hari, S. B.; Perera, B. G.; Ranjitkar, P.; Seeliger, M. A.; Maly, D. J. Conformation-selective Inhibitors Reveal Differences in the Activation and Phosphate-binding Loops of the Tyrosine Kinases Abl and Src ACS Chem. Biol. 2013, 8, 2734-2743 10.1021/cb400663k
58. Agafonov, R. V.; Wilson, C.; Otten, R.; Buosi, V.; Kern, D. Energetic Dissection of Gleevec's Selectivity Toward Human Tyrosine Kinases Nat. Struct. Mol. Biol. 2014, 21, 848-853 10.1038/nsmb.2891
59. Shan, Y.; Seeliger, M. A.; Eastwood, M. P.; Frank, F.; Xu, H.; Jensen, M.Ø.; Dror, R. O.; Kuriyan, J.; Shaw, D. E. A Conserved Protonation-Dependent Switch Controls Drug Binding in the Abl Kinase Proc. Natl. Acad. Sci. U. S. A. 2009, 106, 139-144 10.1073/pnas.0811223106
60. Dixit, A.; Verkhivker, G. M. Hierarchical Modeling of Activation Mechanisms in the ABL and EGFR Kinase Domains: Thermodynamic and Mechanistic Catalysts of Kinase Activation by Cancer Mutations PLoS Comput. Biol. 2009, 5, e1000487 10.1371/journal.pcbi.1000487
61. Dixit, A.; Verkhivker, G. M. Computational Modeling of Allosteric Communication Reveals Organizing Principles of Mutation-Induced Signaling in ABL and EGFR Kinases PLoS Comput. Biol. 2011, 7, e1002179 10.1371/journal.pcbi.1002179
62. Dölker, N.; Górna, M. W.; Sutto, L.; Torralba, A. S.; Superti-Furga, G.; Gervasio, F. L. The SH2 Domain Regulates c-Abl Kinase Activation by a Cyclin-like Mechanism and Remodulation of the Hinge Motion PLoS Comput. Biol. 2014, 10, e1003863 10.1371/journal.pcbi.1003863
63. Corbi-Verge, C.; Marinelli, F.; Zafra-Ruano, A.; Ruiz-Sanz, J.; Luque, I.; Faraldo-Gómez, J. D. Two-State dynamics of the SH3-SH2 Tandem of Abl Kinase and the Allosteric Role of the N-Cap Proc. Natl. Acad. Sci. U. S. A. 2013, 110, E3372-E3380 10.1073/pnas.1303966110
64. Tsai, C. J.; Sol, A. D.; Nussinov, R. Protein Allostery, Signal Transmission and Dynamics: A Classification Scheme of Allosteric Mechanisms Mol. BioSyst. 2009, 5, 207-216 10.1039/b819720b
65. Tsai, C. J.; Nussinov, R. The Free Energy Landscape in Translational science: How Can Somatic Mutations Result in Constitutive Oncogenic Activation? Phys. Chem. Chem. Phys. 2014, 16, 6332-6341 10.1039/c3cp54253j
66. Vendruscolo, M. N.; Dokholyan, V.; Paci, E.; Karplus, M. Small-World View of the Amino Acids That Play a Key Role in Protein Folding Phys. Rev. E: Stat. Phys., Plasmas, Fluids, Relat. Interdiscip. Top. 2002, 65, 061910 10.1103/PhysRevE.65.061910
67. Dokholyan, N. V.; Li, L.; Ding, F.; Shakhnovich, E. I. Topological Determinants of Protein Folding Proc. Natl. Acad. Sci. U. S. A. 2002, 99, 8637-8641 10.1073/pnas.122076099
68. Atilgan, A. R.; Akan, P.; Baysal, C. Small-World Communication of Residues and Significance for Protein Dynamics Biophys. J. 2004, 86, 85-91 10.1016/S0006-3495(04)74086-2
69. Bagler, G.; Sinha, S. Network Properties of Protein Structures Phys. A 2005, 346, 27-33 10.1016/j.physa.2004.08.046
70. del Sol, A.; O'Meara, P. Small-World Network Approach to Identify Key Residues in Protein-Protein Interaction Proteins: Struct., Funct., Genet. 2005, 58, 672-682 10.1002/prot.20348
71. del Sol, A.; Fujihashi, H.; O'Meara, P. Topology of Small-World Networks of Protein-Protein Complex Structures Bioinformatics 2005, 21, 1311-1315 10.1093/bioinformatics/bti167
72. Sathyapriya, R.; Vijayabaskar, M. S.; Vishveshwara, S. Insights into Protein-DNA Interactions Through Structure Network Analysis PLoS Comput. Biol. 2008, 4, e1000170 10.1371/journal.pcbi.1000170
73. Amitai, G.; Shemesh, A.; Sitbon, E.; Shklar, M.; Netanely, D.; Venger, I.; Pietrokovski, S. Network Analysis of Protein Structures Identifies Functional Residues J. Mol. Biol. 2004, 344, 1135-1146 10.1016/j.jmb.2004.10.055
74. Hu, Z.; Bowen, D.; Southerland, W. M.; del Sol, A.; Pan, Y.; Nussinov, R.; Ma, B. Ligand Binding and Circular Permutation Modify Residue Interaction Network in DHFR PLoS Comput. Biol. 2007, 3, e117 10.1371/journal.pcbi.0030117
75. del Sol, A.; Fujihashi, H.; Amoros, D.; Nussinov, R. Residue Centrality, Functionally Important Residues, and Active Site Shape: Analysis of Enzyme and Non-Enzyme Families Protein Sci. 2006, 15, 2120-2128 10.1110/ps.062249106
76. del Sol, A.; Fujihashi, H.; Amoros, D.; Nussinov, R. Residues Crucial for Maintaining Short Paths in Network Communication Mediate Signaling in Proteins Mol. Syst. Biol. 2006, 2, 2006.0019 10.1038/msb4100063
77. Brinda, K. V.; Vishveshwara, S. A Network Representation of Protein Structures: Implications for Protein Stability Biophys. J. 2005, 89, 4159-4170 10.1529/biophysj.105.064485
78. Vijayabaskar, M. S.; Vishveshwara, S. Interaction Energy Based Protein Structure Networks Biophys. J. 2010, 99, 3704-3715 10.1016/j.bpj.2010.08.079
79. Ghosh, A.; Vishveshwara, S. A Study of Communication Pathways in Methionyl-tRNA Synthetase by Molecular Dynamics Simulations and Structure Network Analysis Proc. Natl. Acad. Sci. U. S. A. 2007, 104, 15711-15716 10.1073/pnas.0704459104
80. Ghosh, A.; Vishveshwara, S. Variations in Clique and Community Patterns in Protein Structures During Allosteric Communication: Investigation of Dynamically Equilibrated Structures of Methionyl tRNA Synthetase Complexes Biochemistry 2008, 47, 11398-11407 10.1021/bi8007559
81. Bhattacharyya, M.; Vishveshwara, S. Elucidation of the Conformational Free Energy Landscape in H.pylori LuxS and Its Implications to Catalysis BMC Struct. Biol. 2010, 10, 27 10.1186/1472-6807-10-27
82. Bhattacharyya, M.; Vishveshwara, S. Probing the Allosteric Mechanism in Pyrrolysyl-tRNA Synthetase Using Energy-Weighted Network Formalism Biochemistry 2011, 50, 6225-6236 10.1021/bi200306u
83. Sethi, A.; Eargle, J.; Black, A. A.; Luthey-Schulten, Z. Dynamical Networks in tRNA:Protein Complexes Proc. Natl. Acad. Sci. U. S. A. 2009, 106, 6620-6625 10.1073/pnas.0810961106
84. Ghosh, A.; Sakaguchi, R.; Liu, C.; Vishveshwara, S.; Hou, Y. M. Allosteric Communication in Cysteinyl tRNA Synthetase: A Network of Direct and Indirect Readout J. Biol. Chem. 2011, 286, 37721-37731 10.1074/jbc.M111.246702
85. Rivalta, I.; Sultan, M. M.; Lee, N. S.; Manley, G. A.; Loria, J. P.; Batista, V. S. Allosteric Pathways in Imidazole Glycerol Phosphate Synthase Proc. Natl. Acad. Sci. U. S. A. 2012, 109, E1428-E1436 10.1073/pnas.1120536109
86. Pfleger, C.; Rathi, P. C.; Klein, D. L.; Radestock, S.; Gohlke, H. Constraint Network Analysis (CNA): A Python Software Package for Efficiently Linking Biomacromolecular Structure, Flexibility, (Thermo-)stability, and Function J. Chem. Inf. Model. 2013, 53, 1007-1015 10.1021/ci400044m
87. Krüger, D. M.; Rathi, P. C.; Pfleger, C.; Gohlke, H. CNA Web Server: Rigidity Theory-based Thermal Unfolding Simulations of Proteins for Linking Structure, Flexibility, (Thermo-)stability, and Function Nucleic Acids Res. 2013, 41, W340-W348 10.1093/nar/gkt292
88. Pfleger, C.; Gohlke, H. Efficient and Robust Analysis of Biomacromolecular Flexibility Using Ensembles of Network Topologies Based on Fuzzy Noncovalent Constraints Structure 2013, 21, 1725-1734 10.1016/j.str.2013.07.012
89. Berman, H. M.; Westbrook, J.; Feng, Z.; Gilliland, G.; Bhat, T. N.; Weissig, H.; Shindyalov, I. N.; Bourne, P. E. The Protein Data Bank Nucleic Acids Res. 2000, 28, 235-242 10.1093/nar/28.1.235
90. Fernandez-Fuentes, N.; Zhai, J.; Fiser, A. ArchPRED: A Template Based Loop Structure Prediction Server Nucleic Acids Res. 2006, 34, W173-W176 10.1093/nar/gkl113
91. Phillips, J. C.; Braun, R.; Wang, W.; Gumbart, J.; Tajkhorshid, E.; Villa, E.; Chipot, C.; Skeel, R. D.; Kalé, L.; Schulten, K. Scalable Molecular Dynamics with NAMD J. Comput. Chem. 2005, 26, 1781-1802 10.1002/jcc.20289
92. MacKerell, A. D.; Bashford, D.; Bellott, M.; Dunbrack, R. L.; Evanseck, J. D.; Field, M. J.; Fischer, S.; Gao, J.; Guo, H.; Ha, S.; Joseph-McCarthy, D.; Kuchnir, L.; Kuczera, K.; Lau, F. T. K.; Mattos, C.; Michnick, S.; Ngo, T.; Nguyen, D. T.; Prodhom, B.; Reiher, W. E.; Roux, B.; Schlenkrich, M.; Smith, J. C.; Stote, R.; Straub, J.; Watanabe, M.; Wiórkiewicz-Kuczera, J.; Yin, D.; Karplus, M. All-Atom Empirical Potential for Molecular Modeling and Dynamics Studies of Proteins J. Phys. Chem. B 1998, 102, 3586-3616 10.1021/jp973084f
93. James, K. A.; Verkhivker, G. M. Structure-Based network Analysis of Activation Mechanisms in the ErbB Family of Receptor Tyrosine Kinases: The Regulatory Spine Residues are Global Mediators of Structural Stability and Allosteric Interactions PLoS One 2014, 9, e113488 10.1371/journal.pone.0113488
94. Koukos, P. I.; Glykos, N. M. Grcarma: A Fully Automated Task-Oriented Interface for the Analysis of Molecular Dynamics Trajectories J. Comput. Chem. 2013, 34, 2310-2312 10.1002/jcc.23381
95. Fraczkiewicz, R.; Braun, W. Exact and Efficient Analytical Calculation of the Accessible Surface Areas and Their Gradients for Macromolecules J. Comput. Chem. 1998, 19, 319-333 10.1002/(SICI)1096-987X(199802)19:3<319::AID-JCC6>3.0.CO;2-W
96. Tan, K. P.; Nguyen, T. B.; Patel, S.; Varadarajan, R.; Madhusudhan, M. S. Depth: A Web Server to Compute Depth, Cavity Sizes, Detect Potential Small-Molecule Ligand-Binding Cavities and Predict the pKa of Ionizable Residues in Proteins Nucleic Acids Res. 2013, 41, W314-W321 10.1093/nar/gkt503
97. Floyd, R. W. Algorithm 97: Shortest Path Commun. ACM 1962, 5, 345 10.1145/367766.368168
98. Márquez, J. A.; Smith, C. I. E.; Petoukhov, M. V.; Surdo, Lo. P.; Mattsson, P. T.; Knekt, M.; Westlund, A.; Scheffzek, K.; Saraste, M.; Svergun, D. I. Conformation of Full-Length Bruton Tyrosine Kinase (Btk) from Synchrotron X-ray Solution Scattering EMBO J. 2003, 22, 4616-4624 10.1093/emboj/cdg448
99. Manley, G.; Rivalta, I.; Loria, J. P. Solution NMR and Computational Methods for Understanding Protein Allostery J. Phys. Chem. B 2013, 117, 3063-3073 10.1021/jp312576v
100. Illingworth, C. J.; Scott, P. D.; Parkes, K. E.; Snell, C. R.; Campbell, M. P.; Reynolds, C. A. Connectivity and Binding Site Recognition: Applications Relevant to Drug Design J. Comput. Chem. 2010, 31, 2677-2688 10.1002/jcc.21561
101. Nagar, B. C-Abl Tyrosine kinase and Inhibition by the Cancer Drug Imatinib (Gleevec/STI-571) J. Nutr. 2007, 137, 1518S-1523S
102. Gonfloni, S.; Weijland, A.; Kretzschmar, J.; Superti-Furga, G. Crosstalk Between the Catalytic and Regulatory Domains Allows Bidirectional Regulation of Src Nat. Struct. Biol. 2000, 7, 281-286 10.1038/74041
103. LaFevre-Bernt, M.; Sicheri, F.; Pico, A.; Porter, M.; Kuriyan, J.; Miller, W. T. Intramolecular Regulatory Interactions in the Src Family Kinase Hck Probed by Mutagenesis of A Conserved Tryptophan Residue J. Biol. Chem. 1998, 273, 32129-32134 10.1074/jbc.273.48.32129
104. Gonfloni, S.; Frischknecht, F.; Way, M.; Superti-Furga, G. Leucine 255 of Src Couples Intramolecular Interactions to Inhibition of Catalysis Nat. Struct. Biol. 1999, 6, 760-764 10.1038/11537
105. Colizza, V.; Flammini, A.; Serrano, M. A.; Vespignani, A. Detecting Rich-Club Ordering in Complex Networks Nat. Phys. 2006, 2, 110-115 10.1038/nphys209
106. Bagler, G.; Sinha, S. Assortative Mixing in Protein Contact Networks and Protein Folding Kinetics Bioinformatics 2007, 23, 1760-1767 10.1093/bioinformatics/btm257