Novel allosteric sites on ras for lead generation

PLoS ONE

Volumn 6, Issue 10, 2011, Pages

  Grant, Barry J ^a   Lukman, Suryani ^c,d   Hocker, Harrison J ^e   Sayyah, Jaqueline ^b   Brown, Joan Heller ^b   McCammon, J Andrew ^b   Gorfe, Alemayehu A ^e  

^a UNIVERSITY OF MICHIGAN   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c BIOINFORMATICS INSTITUTE   (Singapore)

^d UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^e UNIVERSITY OF TEXAS MEDICAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ENZYME INHIBITOR; RAS INHIBITOR; RAS PROTEIN; UNCLASSIFIED DRUG; NUCLEOTIDE;

ALLOSTERISM; ARTICLE; CELL ASSAY; CONTROLLED STUDY; CRYSTAL STRUCTURE; DRUG BINDING SITE; DRUG MECHANISM; DRUG SCREENING; DRUG STRUCTURE; ENZYME CONFORMATION; ENZYME INHIBITION; EXPERIMENTAL TEST; GLIOBLASTOMA; GLIOMA CELL; MATHEMATICAL COMPUTING; MOLECULAR DOCKING; MOLECULAR DYNAMICS; MOLECULAR LIBRARY; NUCLEOTIDE BINDING SITE; PROCESS DEVELOPMENT; PROTEIN EXPRESSION; SIGNAL TRANSDUCTION; STRUCTURAL BIOINFORMATICS; VIRTUAL REALITY; BINDING SITE; BIOLOGY; CELL LINE; CHEMICAL STRUCTURE; CHEMISTRY; COMPUTER SIMULATION; DRUG ANTAGONISM; DRUG DESIGN; DRUG EFFECT; HUMAN; METABOLISM; PROTEIN BINDING;

ALLOSTERIC SITE; CELL LINE; COMPUTATIONAL BIOLOGY; COMPUTER SIMULATION; DRUG DESIGN; HUMANS; MODELS, MOLECULAR; NUCLEOTIDES; PROTEIN BINDING; RAS PROTEINS; SIGNAL TRANSDUCTION; SMALL MOLECULE LIBRARIES;

EID: 80055034617     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0025711     Document Type: Article

References (77)

1. Karnoub AE, Weinberg RA, (2008) Ras oncogenes: split personalities. Nat Rev Mol Cell Biol 9: 517-531.
2. Gorfe AA, (2010) Mechanisms of allostery and membrane attachment in Ras GTPases: implications for anti-cancer drug discovery. Curr Med Chem 17: 1-9.
3. Gremer L, Merbitz-Zahradnik T, Dvorsky R, Cirstea IC, Kratz CP, et al. (2011) Germline KRAS mutations cause aberrant biochemical and physical properties leading to developmental disorders. Hum Mutat 32: 33-43.
4. Rauen KA, Schoyer L, McCormick F, Lin AE, Allanson JE, et al. (2010) Proceedings from the 2009 genetic syndromes of the Ras/MAPK pathway: From bedside to bench and back. Am J Med Genet A 152A: 4-24.
5. Cirstea IC, Kutsche K, Dvorsky R, Gremer L, Carta C, et al. (2010) A restricted spectrum of NRAS mutations causes Noonan syndrome. Nat Genet 42: 27-29.
6. Schubbert S, Shannon K, Bollag G, (2007) Hyperactive Ras in developmental disorders and cancer. Nat Rev Cancer 7: 295-308.
7. Sebti SM, Hamilton AD, (2000) Farnesyltransferase and geranylgeranyltransferase I inhibitors in cancer therapy: important mechanistic and bench to bedside issues. Expert Opin Investig Drugs 9: 2767-2782.
8. Kohl NE, Omer CA, Conner MW, Anthony NJ, Davide JP, et al. (1995) Inhibition of farnesyltransferase induces regression of mammary and salivary carcinomas in ras transgenic mice. Nat Med 1: 792-797.
9. James GL, Goldstein JL, Brown MS, (1995) Polylysine and CVIM sequences of K-RasB dictate specificity of prenylation and confer resistance to benzodiazepine peptidomimetic in vitro. J Biol Chem 270: 6221-6226.
10. Lobell RB, Omer CA, Abrams MT, Bhimnathwala HG, Brucker MJ, et al. (2001) Evaluation of farnesyl:protein transferase and geranylgeranyl:protein transferase inhibitor combinations in preclinical models. Cancer Res 61: 8758-8768.
11. Roberts PJ, Der CJ, (2007) Targeting the Raf-MEK-ERK mitogen-activated protein kinase cascade for the treatment of cancer. Oncogene 26: 3291-3310.
12. Bollag G, Freeman S, Lyons JF, Post LE, (2003) Raf pathway inhibitors in oncology. Curr Opin Investig Drugs 4: 1436-1441.
13. Hardy JA, Wells JA, (2004) Searching for new allosteric sites in enzymes. Curr Opin Struct Biol 14: 706-715.
14. Cox AD, Channing JD, (2002) Ras family signaling. Cancer Biol Ther 1: 599-606.
15. Brummelkamp TR, Bernards R, Agami R, (2002) Stable suppression of tumorigenicity by virus-mediated RNA interference. Cancer Cell 2: 243-247.
16. Fleming JB, Shen GL, Holloway SE, Davis M, Brekken RA, (2005) Molecular consequences of silencing mutant K-ras in pancreatic cancer cells: justification for K-ras-directed therapy. Mol Cancer Res 3: 413-423.
17. Chen X, Guo X, Zhang H, Xiang Y, Chen J, et al. (2009) Role of miR-143 targeting KRAS in colorectal tumorigenesis. Oncogene 28: 1385-1392.
18. Zhao WG, Yu SN, Lu ZH, Ma YH, Gu YM, et al. (2010) The miR-217 microRNA functions as a potential tumor suppressor in pancreatic ductal adenocarcinoma by targeting KRAS. Carcinogenesis 31: 1726-1733.
19. Aoki K, Ohnami S, Yoshida T, (2005) Suppression of pancreatic and colon cancer cells by antisense K-ras RNA expression vectors. Methods Mol Med 106: 193-204.
20. Barbacid M, (1987) ras genes. Annu Rev Biochem 56: 779-827.
21. Abankwa D, Gorfe AA, Inder K, Hancock JF, (2010) Ras membrane orientation and nanodomain localization generate isoform diversity. Proc Natl Acad Sci U S A 107: 1130-1135.
22. Abankwa D, Hanzal-Bayer M, Ariotti N, Plowman SJ, Gorfe AA, et al. (2008) A novel switch region regulates H-ras membrane orientation and signal output. EMBO J 27: 727-735.
23. Gorfe AA, Grant BJ, McCammon JA, (2008) Mapping the nucleotide and isoform-dependent structural and dynamical features of Ras proteins. Structure 16: 885-896.
24. Lukman S, Grant BJ, Gorfe AA, Grant GH, McCammon JA, (2010) The distinct conformational dynamics of K-Ras and H-Ras A59G. PLoS Comput Biol 6.
25. Abankwa D, Gorfe AA, Hancock JF, (2008) Mechanisms of Ras membrane organization and signalling: Ras on a rocker. Cell Cycle 7: 2667-2673.
26. Futatsugi N, Tsuda M, (2001) Molecular dynamics simulations of Gly-12→Val mutant of p21(ras): dynamic inhibition mechanism. Biophys J 81: 3483-3488.
27. Carlson HA, McCammon JA, (2000) Accommodating Protein Flexibility in Computational Drug Design. Mol Pharmacol 57: 213-218.
28. Teague SJ, (2003) Implications of protein flexibility for drug discovery. Nat Rev Drug Discov 2: 527-541.
29. Lin JH, Perryman AL, Schames JR, McCammon JA, (2002) Computational drug design accommodating receptor flexibility: the relaxed complex scheme. J Am Chem Soc 124: 5632-5633.
30. Amaro RE, Baron R, McCammon JA, (2008) An improved relaxed complex scheme for receptor flexibility in computer-aided drug design. J Comput Aided Mol Des 22: 693-705.
31. Cheng LS, Amaro RE, Xu D, Li WW, Arzberger PW, et al. (2008) Ensemble-based virtual screening reveals potential novel antiviral compounds for avian influenza neuraminidase. J Med Chem 51: 3878-3894.
32. Laine E, Goncalves C, Karst JC, Lesnard A, Rault S, et al. (2010) Use of allostery to identify inhibitors of calmodulin-induced activation of Bacillus anthracis edema factor. Proc Natl Acad Sci U S A 107: 11277-11282.
33. Chang L, Miyata Y, Ung PM, Bertelsen EB, McQuade TJ, et al. (2011) Chemical screens against a reconstituted multiprotein complex: myricetin blocks DnaJ regulation of DnaK through an allosteric mechanism. Chem Biol 18: 210-221.
34. Gao Y, Dickerson JB, Guo F, Zheng J, Zheng Y, (2004) Rational design and characterization of a Rac GTPase-specific small molecule inhibitor. Proc Natl Acad Sci U S A 101: 7618-7623.
35. Jayakanthan M, Wadhwa G, Mohan T, Arul L, Balasubramanian P, et al. (2009) Computer-aided drug design for cancer-causing H-ras p21 mutant protein. Lett Drug Des Discov 6: 14-20.
36. Grant BJ, Rodrigues AP, ElSawy KM, McCammon JA, Caves LS, (2006) Bio3d: an R package for the comparative analysis of protein structures. Bioinformatics 22: 2695-2696.
37. Grant BJ, McCammon JA, Caves LS, Cross RA, (2007) Multivariate analysis of conserved sequence-structure relationships in kinesins: coupling of the active site and a tubulin-binding sub-domain. J Mol Biol 368: 1231-1248.
38. Downward J, (2003) Targeting RAS signalling pathways in cancer therapy. Nat Rev Cancer 3: 11-22.
39. Friday BB, Adjei AA, (2005) K-ras as a target for cancer therapy. Biochim Biophys Acta 1756: 127-144.
40. Wong CF, McCammon JA, (2003) Protein flexibility and computer-aided drug design. Annu Rev Pharmacol Toxicol 43: 31-45.
41. Perot S, Sperandio O, Miteva MA, Camproux AC, Villoutreix BO, (2010) Druggable pockets and binding site centric chemical space: a paradigm shift in drug discovery. Drug Discov Today 15: 656-667.
42. Brenke R, Kozakov D, Chuang GY, Beglov D, Hall D, et al. (2009) Fragment-based identification of druggable 'hot spots' of proteins using Fourier domain correlation techniques. Bioinformatics 25: 621-627.
43. Grant BJ, Gorfe AA, McCammon JA, (2009) Ras conformational switching: simulating nucleotide-dependent conformational transitions with accelerated molecular dynamics. PLoS Comput Biol 5: e1000325.
44. Harris R, Olson AJ, Goodsell DS, (2008) Automated prediction of ligand-binding sites in proteins. Proteins 70: 1506-1517.
45. Wang Q, Pang YP, (2007) Preference of small molecules for local minimum conformations when binding to proteins. PLoS One 2: e820.
46. Henrich S, Salo-Ahen OM, Huang B, Rippmann FF, Cruciani G, et al. (2010) Computational approaches to identifying and characterizing protein binding sites for ligand design. J Mol Recognit 23: 209-219.
47. Friesner RA, Banks JL, Murphy RB, Halgren TA, Klicic JJ, et al. (2004) Glide: a new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy. J Med Chem 47: 1739-1749.
48. Halgren TA, Murphy RB, Friesner RA, Beard HS, Frye LL, et al. (2004) Glide: a new approach for rapid, accurate docking and scoring. 2. Enrichment factors in database screening. J Med Chem 47: 1750-1759.
49. Schames JR, Henchman RH, Siegel JS, Sotriffer CA, Ni H, et al. (2004) Discovery of a novel binding trench in HIV integrase. J Med Chem 47: 1879-1881.
50. Furnari FB, Lin H, Huang HS, Cavenee WK, (1997) Growth suppression of glioma cells by PTEN requires a functional phosphatase catalytic domain. Proc Natl Acad Sci U S A 94: 12479-12484.
51. Gorfe AA, Babakhani A, McCammon JA, (2007) H-ras protein in a bilayer: interaction and structure perturbation. J Am Chem Soc 129: 12280-12286.
52. Buhrman G, Holzapfel G, Fetics S, Mattos C, (2010) Allosteric modulation of Ras positions Q61 for a direct role in catalysis. Proc Natl Acad Sci U S A 107: 4931-4936.
53. Spoerner M, Graf T, Konig B, Kalbitzer HR, (2005) A novel mechanism for the modulation of the Ras-effector interaction by small molecules. Biochem Biophys Res Commun 334: 709-713.
54. Rosnizeck IC, Graf T, Spoerner M, Trankle J, Filchtinski D, et al. (2010) Stabilizing a weak binding state for effectors in the human ras protein by cyclen complexes. Angew Chem Int Ed Engl 49: 3830-3833.
55. Grant BJ, Gorfe AA, McCammon JA, (2010) Large conformational changes in proteins: signaling and other functions. Curr Opin Struct Biol.
56. Szczepankiewicz BG, Liu G, Hajduk PJ, Abad-Zapatero C, Pei Z, et al. (2003) Discovery of a potent, selective protein tyrosine phosphatase 1B inhibitor using a linked-fragment strategy. J Am Chem Soc 125: 4087-4096.
57. Formaneck MS, Ma L, Cui Q, (2006) Reconciling the "old" and "new" views of protein allostery: a molecular simulation study of chemotaxis Y protein (CheY). Proteins 63: 846-867.
58. McClendon CL, Friedland G, Mobley DL, Amirkhani H, Jacobson MP, (2009) Quantifying Correlations Between Allosteric Sites in Thermodynamic Ensembles. J Chem Theory Comput 5: 2486-2502.
59. Gsponer J, Christodoulou J, Cavalli A, Bui JM, Richter B, et al. (2008) A coupled equilibrium shift mechanism in calmodulin-mediated signal transduction. Structure 16: 736-746.
60. Fukunishi Y, Nakamura H, (2011) Prediction of ligand-binding sites of proteins by molecular docking calculation for a random ligand library. Protein Sci 20: 95-106.
61. Morris GM, Goodsell DS, Halliday RS, Huey R, Hart WE, et al. (1998) Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function. J Comp Chem 19: 1639-1662.
62. Lipinski CA, Lombardo F, Dominy BW, Feeney PJ, (2001) Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev 46: 3-26.
63. Durrant JD, de Oliveira CA, McCammon JA, (2011) POVME: an algorithm for measuring binding-pocket volumes. J Mol Graph Model 29: 773-776.
64. Dolinsky TJ, Nielsen JE, McCammon JA, Baker NA, (2004) PDB2PQR: an automated pipeline for the setup, execution, and analysis of Poisson-Boltzmann electrostatics calculations. Nucleic Acids Res 32: W665-W667.
65. Case DA, Darden TA, Cheatham TE III, Simmerling CL, Wang J, et al. (2008) AMBER 10. University of California, San Francisco.
66. Hornak V, Abel R, Okur A, Strockbine B, Roitberg A, et al. (2006) Comparison of multiple Amber force fields and development of improved protein backbone parameters. Proteins 65: 712-725.
67. Meagher KL, Redman LT, Carlson HA, (2003) Development of polyphosphate parameters for use with the AMBER force field. J Comput Chem 24: 1016-1025.
68. van Gunsteren WF, Berendsen HJ, (1977) Algorithms for macromolecular dynamics and constraint dynamics. Molecular Physics 34: 1311-1327.
69. Darden T, York D, Pedersen L, (1993) Particle mesh Ewald-an NlogN method for Ewald sums in large systems. J Chem Phys 98: 10089-10092.
70. Gehlhaar DK, Verkhivker GM, Rejto PA, Sherman CJ, Fogel DB, et al. (1995) Molecular recognition of the inhibitor AG-1343 by HIV-1 protease: conformationally flexible docking by evolutionary programming. Chem Biol 2: 317-324.
71. Jain AN, (1996) Scoring noncovalent protein-ligand interactions: a continuous differentiable function tuned to compute binding affinities. J Comput Aided Mol Des 10: 427-440.
72. Muegge I, Martin YC, (1999) A general and fast scoring function for protein-ligand interactions: a simplified potential approach. J Med Chem 42: 791-804.
73. Muegge I, (2006) PMF scoring revisited. J Med Chem 49: 5895-5902.
74. Bohm HJ, (1994) The development of a simple empirical scoring function to estimate the binding constant for a protein-ligand complex of known three-dimensional structure. J Comput Aided Mol Des 8: 243-256.
75. Bohm HJ, (1992) LUDI: rule-based automatic design of new substituents for enzyme inhibitor leads. J Comput Aided Mol Des 6: 593-606.
76. Bohm HJ, (1998) Prediction of binding constants of protein ligands: a fast method for the prioritization of hits obtained from de novo design or 3D database search programs. J Comput Aided Mol Des 12: 309-323.
77. Pickett SD, McLay IM, Clark DE, (2000) Enhancing the hit-to-lead properties of lead optimization libraries. J Chem Inf Comput Sci 40: 263-272.