Hierarchical modeling of activation mechanisms in the ABL and EGFR kinase domains: Thermodynamic and mechanistic catalysts of kinase activation by cancer mutations

PLoS Computational Biology

Volumn 5, Issue 8, 2009, Pages

  Dixit, Anshuman ^a   Verkhivker, Gennady M ^a,b,c  

^a UNIVERSITY OF KANSAS   (United States)

^b UNIVERSITY OF KANSAS   (United States)

^c UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ACTIVATION ANALYSIS; COMPUTATIONAL CHEMISTRY; DISEASES; ENZYMES; MOLECULAR DYNAMICS; STABILIZATION; THERMODYNAMICS;

ACTIVATION MECHANISMS; CONFORMATIONAL THERMODYNAMICS; CONFORMATIONAL TRANSITIONS; DYNAMIC ASPECTS; HIERARCHICAL MODEL; KINASE ACTIVATION; KINASE DOMAINS; MECHANISTIC ASPECTS; MECHANISTICS; ]+ CATALYST;

CHEMICAL ACTIVATION;

ABELSON KINASE; EPIDERMAL GROWTH FACTOR RECEPTOR; PROTEIN KINASE;

ARTICLE; CATALYST; GENE MUTATION; NEOPLASM; NUCLEAR MAGNETIC RESONANCE; PROTEIN ANALYSIS; PROTEIN STABILITY; THERMODYNAMICS; BIOLOGY; CATALYSIS; CHEMISTRY; COMPUTER SIMULATION; CONFORMATION; DRUG ANTAGONISM; GENE EXPRESSION REGULATION; GENETICS; HUMAN; METHODOLOGY; MUTATION; PROTEIN CONFORMATION; PROTEIN TERTIARY STRUCTURE; TUMOR CELL LINE; X RAY CRYSTALLOGRAPHY;

PYRONIA TITHONUS;

CATALYSIS; CELL LINE, TUMOR; COMPUTATIONAL BIOLOGY; COMPUTER SIMULATION; CRYSTALLOGRAPHY, X-RAY; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; MOLECULAR CONFORMATION; MUTATION; NEOPLASMS; PROTEIN CONFORMATION; PROTEIN STRUCTURE, TERTIARY; PROTO-ONCOGENE PROTEINS C-ABL; RECEPTOR, EPIDERMAL GROWTH FACTOR; THERMODYNAMICS;

EID: 70149117469     PISSN: 1553734X     EISSN: 15537358     Source Type: Journal    
DOI: 10.1371/journal.pcbi.1000487     Document Type: Article

References (112)

1. Hanks SK, Hunter T (1995) The eukaryotic protein kinase superfamily: kinase (catalytic) domain structure and classification. FASEB J 9: 576-596.
2. Hunter T, Plowman GD (1997) Review: the protein kinases of budding yeast: six score and more. Trends Biochem Sci 22: 18-22. (Pubitemid 27056092)
3. Manning G, Whyte DB, Martinez R, Hunter T, Sudarsanam S (2002) The protein kinase complement of the human genome. Science 298: 1912-1934. (Pubitemid 35425239)
4. Manning G, Plowman GD, Hunter T, Sudarsanam S (2002) Evolution of protein kinase signaling from yeast to man. Trends Biochem Sci 10: 514-520. (Pubitemid 35279596)
5. Hunter T (2000) Signaling - 2000 and beyond. Cell 100: 113-127.
6. Johnson LN, Noble ME, Owen DJ (1996) Active and inactive protein kinases: structural basis for regulation. Cell 85: 149-158. (Pubitemid 26118158)
7. Noble ME, Endicott JA, Johnson LN (2004) Protein kinase inhibitors: insights into drug design from structure. Science 303: 1800-1805. (Pubitemid 38374863)
8. Cherry M, DH (2004) Recent kinase and kinase inhibitor X-ray structures: mechanisms of inhibition and selectivity insights. Curr Med Chem 11: 663-673.
9. Cheetham GM (2004) Novel protein kinases and molecular mechanisms of autoinhibition. Curr Opin Struct Biol 14: 700-705. (Pubitemid 39592581)
10. Schindler T, Bornmann W, Pellicena P, Miller WT, Clarkson B, et al. (2000) Structural mechanism for STI-571 inhibition of abelson tyrosine kinase. Science 289: 1938-1942. (Pubitemid 30704121)
11. Nagar B, Bornmann WG, Pellicena P, Schindler T, Veach DR, et al. (2002) Crystal structures of the kinase domain of c- Abl in complex with the small molecule inhibitors PD173955 and imatinib (STI-571). Cancer Res 62: 4236-4243. (Pubitemid 34827278)
12. Azam M, Latek RR, Daley GQ (2003) Mechanisms of autoinhibition and STI-571/imatinib resistance revealed by mutagenesis of BCR-ABL. Cell 112: 831-843. (Pubitemid 36378885)
13. Nagar B, Hantschel O, Young MA, Scheffzek K, Veach DR, et al. (2003) Structural basis for the autoinhibition of c-Abl tyrosine kinase. Cell 112: 859-871. (Pubitemid 36378887)
14. Atwell S, Adams JM, Badger J, Buchanan MD, Feil IK, et al. (2004) A novel mode of Gleevec binding is revealed by the structure of spleen tyrosine kinase. J Biol Chem 279: 55827-55832. (Pubitemid 40066590)
15. Mol CD, Dougan DR, Schneider TR, Skene RJ, Kraus ML, et al. (2004) Structural basis for the autoinhibition and STI-571 inhibition of c-Kit tyrosine kinase. J Biol Chem 279: 31655-31663.
16. Cowan-Jacob SW, Fendrich G, Manley PW, Jahnke W, Fabbro D, et al. (2005) The crystal structure of a c-Src complex in an active conformation suggests possible steps in c-Src activation. Structure 13: 861-871. (Pubitemid 40804389)
17. Nagar B, Hantschel O, Seeliger M, Davies JM, Weis WI, et al. (2006) Organization of the SH3-SH2 unit in active and inactive forms of the c-Abl tyrosine kinase. Mol Cell 21: 787-798. (Pubitemid 43376129)
18. Levinson NM, Kuchment O, Shen K, Young MA, Koldobskiy M, et al. (2006) A SRC-like inactive conformation in the ABL tyrosine kinase domain. PLoS Biol 4: 0753-0767. (Pubitemid 43748222)
19. Tokarski JS, Newitt JA, Chang CY, Cheng JD, Wittekind M, et al. (2006) The structure of Dasatinib (BMS-354825) bound to activated ABL kinase domain elucidates its inhibitory activity against Imatinib-resistant ABL mutants. Cancer Res 66: 5790-5797. (Pubitemid 43927133)
20. Young MA, Shah NP, Chao LH, Seeliger M, Milanov ZV, et al. (2006) Structure of the kinase domain of an Imatinib-resistant Abl mutant in complex with the Aurora kinase inhibitor VX-680. Cancer Res 6: 1007-1014. (Pubitemid 43168337)
21. Seeliger MA, Nagar B, Frank F, Cao X, Henderson MN, et al. (2007) C-Src binds to the cancer drug imatinib with an inactive Abl/c-Kit conformation and a distributed thermodynamic penalty. Structure 15: 299-311. (Pubitemid 46366721)
22. Stamos J, Sliwkowski MX, Eigenbrot C (2002) Structure of the epidermal growth factor receptor kinase domain alone and in complex with a 4-anilinoquinazoline inhibitor. J Biol Chem 277: 46265-46272. (Pubitemid 35417619)
23. Wood ER, Truesdale AT, McDonald OB, Yuan D, Hassell A, et al. (2004) A unique structure for epidermal growth factor receptor bound to GW572016 (Lapatinib): relationships among protein conformation, inhibitor off-rate, and receptor activity in tumor cells. Cancer Res 64: 6652-6659. (Pubitemid 39297926)
24. Zhang X, Gureasko J, Shen K, Cole PA, Kuriyan J (2006) An allosteric mechanism for activation of the kinase domain of epidermal growth factor receptor. Cell 125: 1137-1149. (Pubitemid 43866200)
25. Huse M, Kuriyan J (2002) The conformational plasticity of protein kinases. Cell 109: 275-282.
26. Nolen B, Taylor SS, Ghosh G (2004) Regulation of protein kinases. Controlling activity through activation segment conformation. Molecular Cell 15: 661-675.
27. Pellicena P, Kuriyan J (2006) Protein-protein interactions in the allosteric regulation of protein kinases. Curr Opin Struct Biol 16: 702-709. (Pubitemid 44834472)
28. Masterson LR, Mascioni A, Traaseth NJ, Taylor SS, Veglia G (2008) Allosteric cooperativity in protein kinase A. Proc Natl Acad Sci U S A 105: 506-511.
29. Kannan N, Neuwald AF (2005) Did protein kinase regulatory mechanisms evolve through elaboration of a simple structural component? J Mol Biol 351: 956-972.
30. Kornev AP, Haste NM, Taylor SS, Eyck LF (2006) Surface comparison of active and inactive protein kinases identifies a conserved activation mechanism. Proc Natl Acad Sci U S A 103: 17783-17788.
31. Ten Eyck LF, Taylor SS, Kornev AP (2008) Conserved spatial patterns across the protein kinase family. Biochim Biophys Acta 1784: 238-243.
32. Kornev AP, Taylor SS, Ten Eyck LF (2008) A helix scaffold for the assembly of active protein kinases. Proc Natl Acad Sci U S A 105: 14377-14382.
33. Sjoblom T, Jones S, Wood LD, Parsons WD, Lin J (2006) The consensus coding sequences of human breast and colorectal cancers. Science 314: 268-274. (Pubitemid 44571966)
34. Wood LD, Parsons DW, Jones S, Lin J, Sjöblom T, et al. (2007) The genomic landscapes of human breast and colorectal cancers. Science 318: 1108-1113. (Pubitemid 350134889)
35. Greenman C, Stephens P, Smith R, Dalgliesh GL, Hunter C, et al. (2007) Patterns of somatic mutation in human cancer genomes. Nature 446: 153-158. (Pubitemid 46398669)
36. Thomas RK, Baker AC, Debiasi RM, Winckler W, Laframboise T, et al. (2007) High-throughput oncogene mutation profiling in human cancer. Nat Genet 39: 347-351. (Pubitemid 46328493)
37. Weinstein BI (2002) Cancer. Addiction to oncogenes-the Achilles heal of cancer. Science 297: 63-64.
38. Sharma SV, Settleman J (2007) Oncogene addiction: setting the stage for molecularly targeted cancer therapy. Genes Dev 21: 3214-3231.
39. Shah NP, Nicoll JM, Nagar B, Gorre ME, Paquette RL, et al. (2002) Multiple BCR-ABL kinase domain mutations confer polyclonal resistance to the tyrosine kinase inhibitor imatinib (STI571) in chronic phase and blast crisis chronic myeloid leukemia. Cancer Cell 2: 117-125. (Pubitemid 41039112)
40. Corbin AS, La Rosee P, Stoffregen EP, Druker BJ, Deininger MW (2003) Several Bcr-Abl kinase domain mutants associated with imatinib mesylate resistance remain sensitive to imatinib. Blood 101: 4611-4614. (Pubitemid 36857835)
41. Shah NP, Tran C, Lee FY, Chen P, Norris D, et al. (2004) Overriding imatinib resistance with a novel ABL kinase inhibitor. Science 305: 399-401. (Pubitemid 38938156)
42. Cowan-Jacob SW, Guez V, Fendrich G, Griffin JD, Fabbro D, et al. (2004) Imatinib (STI571) resistance in chronic myelogenous leukemia: Molecular basis of the underlying mechanisms and potential strategies for treatment. Mini Rev Med Chem 4: 285-299. (Pubitemid 38854871)
43. Wong S, Witte ON (2004) The BCR-ABL story: bench to bedside and back. Annu Rev Immunol 22: 247-306. (Pubitemid 38680424)
44. Seeliger MA, Ranjitkar P, Kasap C, Shan Y, Shaw DE, et al. (2009) Equally potent inhibition of c-Src and Abl by compounds that recognize inactive kinase conformations. Cancer Res 69: 2384-2392.
45. Lynch TJ, Bell DW, Sordella R, Gurubhagavatula S, Okimoto RA, et al. (2004) Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med 350: 2129-2139. (Pubitemid 38637993)
46. Paez JG, Jänne PA, Lee JC, Tracy S, Greulich H, et al. (2004) EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 304: 1497-1500. (Pubitemid 38720929)
47. Pao W, Miller V, Zakowski M, Doherty J, Politi K, et al. (2004) EGF receptor gene mutations are common in lung cancers from "never smokers" and are associated with sensitivity of tumors to gefitinib and erlotinib. Proc Natl Acad Sci USA 101: 13306-13311. (Pubitemid 39209661)
48. Kobayashi S, Boggon TJ, Dayaram T, Jänne PA, Kocher O, et al. (2005) EGFR mutation and resistance of non-small-cell lung cancer to gefitinib. N Engl J Med 352: 786-792. (Pubitemid 40271173)
49. Bell DW, Gore I, Okimoto RA, Godin-Heymann N, Sordella R, et al. (2005) Inherited susceptibility to lung cancer may be associated with the T790M drug resistance mutation in EGFR. Nat Genet 37: 1315-1316. (Pubitemid 41722184)
50. Godin-Heymann N, Bryant I, Rivera MN, Ulkus L, Bell DW, et al. (2007) Oncogenic activity of epidermal growth factor receptor kinase mutant alleles is enhanced by the T790M drug resistance mutation. Cancer Res 67: 7319-7326. (Pubitemid 47206561)
51. Yun CH, Boggon TJ, Li Y, Woo MS, Greulich H, et al. (2007) Structures of lung cancer-derived EGFR mutants and inhibitor complexes: mechanism of activation and insights into differential inhibitor sensitivity. Cancer Cell 11: 217-227. (Pubitemid 46349842)
52. Yun CH, Mengwasser KE, Toms AV, Woo MS, Greulich H, et al. (2008) The T790M mutation in EGFR kinase causes drug resistance by increasing the affinity for ATP. Proc Natl Acad Sci U S A 105: 2070-2075.
53. Kumar A, Petri ET, Halmos B, Boggon TJ (2008) Structure and clinical relevance of the epidermal growth factor receptor in human cancer. J Clin Oncol 26: 1742-1751.
54. Modugno M, Casale E, Soncini C, Rosettani P, Colombo R, et al. (2007) Crystal structure of the T315I Abl mutant in complex with the aurora kinases inhibitor PHA-739358. Cancer Res 67: 7987-7990. (Pubitemid 47395130)
55. Zhou T, Parillon L, Li F, Wang Y, Keats J, et al. (2007) Crystal structure of the T315I mutant of AbI kinase. Chem Biol Drug Des 70: 171-181. (Pubitemid 47305404)
56. Azam M, Seeliger MA, Gray NS, Kuriyan J, Daley GQ (2008) Activation of tyrosine kinases by mutation of the gatekeeper threonine. Nat Struct Mol Biol 15: 1109-1118.
57. Vajpai N, Strauss A, Fendrich G, Cowan-Jacob SW, Manley PW, et al. (2008) Solution conformations and dynamics of ABL kinase-inhibitor complexes determined by NMR substantiate the different binding modes of imatinib/nilotinib and dasatinib. J Biol Chem 283: 18292-18302.
58. Iacob RE, Pene-Dumitrescu T, Zhang J, Gray NS, Smithgall TE, et al. (2009) Conformational disturbance in Abl kinase upon mutation and deregulation. Proc Natl Acad Sci U S A 106: 1386-1391.
59. Young MA, Gonfloni S, Superti-Furga G, Roux B, Kuriyan J (2001) Dynamic coupling between the SH2 and SH3 domains of c-Src and Hck underlies their inactivation by C-terminal tyrosine phosphorylation. Cell 105: 115-126. (Pubitemid 32323921)
60. Mendieta J, Gago F (2004) In silico activation of Src tyrosine kinase reveals the molecular basis for intramolecular autophosphorylation. J Mol Graphics Model 23: 189-198.
61. Ozkirimli E, Post CB (2006) Src kinase activation: A switched electrostatic network. Protein Sci 15: 1051-1062.
62. Ozkirimli E, Yadav SS, Miller WT, Post CB (2008) An electrostatic network and long-range regulation of Src kinases. Protein Sci 17: 1871-1880.
63. Arora K, Brooks CL 3rd (2007) Large-scale allosteric conformational transitions of adenylate kinase appear to involve a population-shift mechanism. Proc Natl Acad Sci U S A 104: 18496-18501.
64. Banavali NK, Roux B (2007) Anatomy of a structural pathway for activation of the catalytic domain of Src kinase Hck. Proteins 67: 1096-1112.
65. Yang S, Roux B (2008) Src kinase conformational activation: Thermodynamics, pathways, and mechanisms. PLoS Comput Biol 4: e1000047.
66. Banavali NK, Roux B (2009) Flexibility and charge asymmetry in the activation loop of Src tyrosine kinases. Proteins 74: 378-389.
67. Yang S, Banavali NK, Roux B (2009) Mapping the conformational transition in Src activation by cumulating the information from multiple molecular dynamics trajectories. Proc Natl Acad Sci U S A 106: 3776-3781.
68. Berteotti A, Cavalli A, Branduardi D, Gervasio FL, Recanatini M, et al. (2009) Protein conformational transitions: the closure mechanism of a kinase explored by atomistic simulations. J Am Chem Soc 131: 244-250.
69. Shan Y, Seeliger MA, Eastwood MP, Frank F, Xu H, Jensen MØ, et al. (2009) A conserved protonation-dependent switch controls drug binding in the Abl kinase. Proc Natl Acad Sci U S A 106: 139-144.
70. Zou J, Wang YD, Ma FX, Xiang ML, Shi B, et al. (2008) Detailed conformational dynamics of juxtamembrane region and activation loop in c-Kit kinase activation process. Proteins 72: 323-332. (Pubitemid 351809170)
71. Papakyriakou A, Vourloumis D, Tzortzatou-Stathopoulou F, Karpusas M (2008) Conformational dynamics of the EGFR kinase domain reveals structural features involved in activation. Proteins 76: 375-386.
72. Dixit A, Torkamani A, Schork NJ, Verkhivker G (2009) Computational modeling of structurally conserved cancer mutations in the RET and MET kinases: the impact on protein structure, dynamics, and stability. Biophys J 96: 858-874.
73. Torkamani A, Verkhivker G, Schork NJ (2009) Cancer Lett 281: 117-127.
74. Ma B, Kumar S, Tsai CJ, Nussinov R (1999) Folding funnels and binding mechanisms. Protein Eng 12: 713-720.
75. Tsai CJ, Kumar S, Ma B, Nussinov R (1999) Folding funnels, binding funnels and protein function. Protein Sci 8: 1181-1190. (Pubitemid 29264948)
76. Tsai CJ, Ma B, Nussinov R (1999) Folding and binding cascades: shifts in energy landscapes. Proc Natl Acad Sci U S A 96: 9970-9972. (Pubitemid 29422488)
77. Kumar S, Ma B, Tsai CJ, Sinha N, Nussinov R (2000) Folding and binding cascades: dynamic landscapes and population shifts. Protein Sci 9: 10-19. (Pubitemid 30070934)
78. Shoemaker BA, Portman JJ, Wolynes PG (2000) Speeding molecular recognition by using the folding funnel: the fly-casting mechanism. Proc Natl Acad Sci U S A 97: 8868-8873.
79. Levy Y, Wolynes PG, Onuchic JN (2004) Protein topology determines binding mechanism. Proc Natl Acad Sci U S A 101: 511-516. (Pubitemid 38084667)
80. Verkhivker GM, Bouzida D, Gehlhaar DK, Rejto PA, Freer ST, et al. (2002) Complexity and simplicity of ligand-macromolecule interactions: the energy landscape perspective. Curr Opin Struct Biol 12: 197-203. (Pubitemid 34327479)
81. Boehr DD, Wright PE (2008) Biochemistry. How do proteins interact? Science 320: 1429-1430.
82. Lange OF, Lakomek NA, Farès C, Schröder GF, Walter KF, et al. (2008) Recognition dynamics up to microseconds revealed from an RDC-derived ubiquitin ensemble in solution. Science 320: 1471-1475.
83. Eisenmesser EZ, Millet O, Labeikovsky W, Korzhnev DM, Wolf-Watz M, et al. (2005) Intrinsic dynamics of an enzyme underlies catalysis. Nature 438: 117-121. (Pubitemid 41599831)
84. Tang C, Schwieters CD, Clore GM (2007) Open-to-closed transition in apo maltose-binding protein observed by paramagnetic NMR. Nature 449: 1078-1082. (Pubitemid 350014601)
85. James LC, Roversi P, Tawfik DS (2003) Antibody multispecificity mediated by conformational diversity. Science 299: 1362-1367. (Pubitemid 36254643)
86. Liu J, Nussinov R (2008) Allosteric effects in the marginally stable von Hippel-Lindau tumor suppressor protein and allostery-based rescue mutant design. Proc Natl Acad Sci U S A 105: 901-906. (Pubitemid 351282053)
87. Thorpe IF, Brooks CL 3rd (2005) Conformational substates modulate hydride transfer in dihydrofolate reductase. J Am Chem Soc 127: 12997-13006
88. Thorpe IF, Brooks CL 3rd (2007) Molecular evolution of affinity and flexibility in the immune system. Proc Natl Acad Sci U S A 104: 8821-8826. (Pubitemid 47175395)
89. Chen S, Brier S, Smithgall TE, Engen JR (2007) The Abl SH2-kinase linker naturally adopts a conformation competent for SH3 domain binding. Protein Sci 16: 572-581. (Pubitemid 46506986)
90. Pluk H, Dorey K, Superti-Furga G (2002) Autoinhibition of c-Abl. Cell 108: 247-259.
91. Strausberg RL, Simpson AJ, Old LJ, Riggins GJ (2004) Oncogenomics and the development of new cancer therapies. Nature 429: 469-474. (Pubitemid 38715142)
92. Strausberg RL, Levy S, Rogers YH (2008) Emerging DNA sequencing technologies for human genomic medicine. Drug Discov Today 13: 569-577.
93. Papadopoulos N, Kinzler KW, Vogelstein B (2006) The role of companion diagnostics in the development and use of mutation-targeted cancer therapies. Nat Biotechnol 24: 985-995. (Pubitemid 44215393)
94. Murdoch D, Sager J (2008) Will targeted therapy hold its promise? An evidence-based review. Curr Opin Oncol 20: 104-111. (Pubitemid 350190989)
95. Marti-Renom MA, Stuart A, Fiser A, Sánchez R, Melo A, et al. (2000) Comparative protein structure modeling of genes and genomes. Annu Rev Biophys Biomol Struct 29: 291-325. (Pubitemid 30599596)
96. Fiser A, Do RK, Sali A (2000) Modeling of loops in protein structures. Protein Science 9: 1753-1773.
97. Canutescu AA, Shelenkov AA, Dunbrack RL Jr (2003) A graph-theory algorithm for rapid protein side-chain prediction. Protein Sci 12: 2001-2014.
98. Phillips JC, Braun R, Wang W, Gumbart J, Tajkhorshid E, et al. (2005) Scalable molecular dynamics with NAMD. J Comput Chem 26: 1781-1802.
99. MacKerell AD Jr, Bashford D, Bellott M, Dunbrack RL Jr, Evanseck JD, et al. (1998) All-atom empirical potential for molecular modeling and dynamics studies of proteins. J Phys Chem B 102: 3586-3616. (Pubitemid 128576688)
100. MacKerell AD Jr, Banavali N, Foloppe N (2001) Development and current status of the CHARMM force field for nucleic acids. Biopolymers 56: 257-265. (Pubitemid 34105873)
101. Jorgensen WL, Chandrasekhar J, Madura JD, Impey RW, Klein ML, et al. (1983) Comparison of simple potential functions for simulating liquid water. J Chem Phys 79: 926-935.
102. Eargle J, Wright D, Luthey-Schulten Z (2006) Multiple alignment of protein structures and sequences for VMD. Bioinformatics 22: 504-506. (Pubitemid 43231430)
103. Essmann U, Perera L, Berkowitz ML, Darden T, Lee H, et al. (1995) A smooth particle mesh Ewald method. J Chem Phys 103: 8577-8593.
104. Wang J, Wolf RM, Caldwell JW, Kollman PA, Case DA (2004) Development and testing of a general amber force field. J Comput Chem 25: 1157-1174.
105. Kollman PA, Massova I, Reyes C, Kuhn B, Huo S, et al. (2000) Calculating structures and free energies of complex molecules: combining molecular mechanics and continuum models. Acc Chem Res 33: 889-897. (Pubitemid 32056774)
106. Onufriev A, Bashford D, Case DA (2000) Modification of the Generalized Born Model suitable for macromolecules. J Phys Chem B 104: 3712-3720. (Pubitemid 30858501)
107. Bashford D, Case DA (2000) Generalized born models of macromolecular solvation effects. Annu Rev Phys Chem 51: 129-152.
108. Homeyer N, Horn AH, Lanig H, Sticht H (2006) AMBER force-field parameters for phosphorylated amino acids in different protonation states: phosphoserine, phosphothreonine, phosphotyrosine, and phosphohistidine. J Mol Model 12: 281-289. (Pubitemid 43337197)
109. Gilson MK, Zhou H-X (2007) Calculation of protein-ligand binding affinities. Annu Rev Biophys Biomol Struct 36: 21-42.
110. Verkhivker GM, Bouzida D, Gehlhaar DK, Rejto PA, Freer ST, et al. (2002) Monte Carlo simulations of the peptide recognition at the consensus binding site of the constant fragment of human immunoglobulin G: the energy landscape analysis of a hot spot at the intermolecular interface. Proteins 48: 539-557. (Pubitemid 34810418)
111. Verkhivker GM, Bouzida D, Gehlhaar DK, Rejto PA, Freer ST, et al. (2003) Computational detection of the binding-site hot spot at the remodeled human growth hormone-receptor interface. Proteins 53: 201-219. (Pubitemid 37193816)
112. Beutler TC, Mark AE, van Schaik RC, Gerber PR, van Gunsteren W (1994) Avoiding singularities and numerical instabilities in free energy calculations base on molecular simulations. Chem Phys Lett 222: 529-539.