A novel ensemble-based scoring and search algorithm for protein redesign, and its application to modify the substrate specificity of the gramicidin synthetase a phenylalanine adenylation enzyme

Proceedings of the Annual International Conference on Computational Molecular Biology, RECOMB

Volumn 8, Issue , 2004, Pages 46-57

  Lilien, Ryan H ^a,b,c   Stevens, Brian W ^c,d   Andersen, Amy C ^c,e   Donald, Bruce R ^a,b,e,f  

^a Dartmouth College   (United States)

^b DARTMOUTH MEDICAL SCHOOL   (United States)

^c Dartmouth Ctr Struct Biol/CC   (United States)

^d Dartmouth Department of Biochemistry   (United States)

^e Lamont Doherty Earth Observatory   (United States)

^f Dartmouth Department of Biology   (United States)

Author keywords

Enzyme design; Fluorescence binding assay; Molecular ensemble; Non ribosomal peptide synthetase; Protein design; Protein flexibility; Protein ligand binding

Indexed keywords

ALGORITHMS; BIOASSAY; COMPUTATIONAL COMPLEXITY; DRUG PRODUCTS; ENZYMES; FLUORESCENCE; GENETIC ENGINEERING; MOLECULAR STRUCTURE; PROBLEM SOLVING;

ENZYME DESIGN; FLUORESCENCE BINDING ASSAY; MOLECULAR ENSEMBLE; NON-RIBOSOMAL PROTEIN SYNTHETASE; PROTEIN DESIGN; PROTEIN FLEXIBILITY; PROTEIN LIGANDS;

COMPUTER SCIENCE;

EID: 2442451469     PISSN: None     EISSN: None     Source Type: Conference Proceeding    
DOI: 10.1145/974614.974622     Document Type: Conference Paper

References (56)

1. BELSHAW, P., WALSH, C., AND STACHELHAUS, T. Aminoacyl-CoAs as probes of condensation domain selectivity in nonribosomal peptide synthesis. Science 284 (1999), 486-489.
2. BÖHM, H. On the use of LUDI to search the fine chemicals directory for ligands of proteins of known three-dimensional structure. J. Comput. Aided Mol. Des. 8 (1994), 623-632.
3. BOLON, D., AND MAYO, S. Enzyme-like proteins by computational design. Proc. Natl. Acad. Sci. USA 98 (2001), 14274-14279.
4. BOUZIDA, D., REJTO, P., ARTHURS, S., COLSON, A., FREER, S., GEHLHAAR, D., LARSON, V., LUTY, B., ROSE, P., AND VERKHIVKER, O. Computer simulations of ligand-protein binding with ensembles of protein conformations: A monte carlo study of HIV-1 protease binding energy landscapes. Int. J. Quantum Chem. 72(1999), 73-84.
5. CANE, D., WALSH, C., AND KHOSLA, C. Harnessing the biosynthetic code: combinations, permutations, and mutations. Science 282 (1998), 63-68.
6. CARLSON, H. Protein flexibility and drug design: how to hit a moving target. Curr. Opin. Chem. Biol. 6 (2002), 447-452.
7. CHALLIS, G., RAVEL, J., AND TOWNSEND, C. Predictive, structure-based model of amino acid recognition by nonribosomal peptide synthetase adenylation domains. Chem. Biol. 7 (2000), 211-224.
8. CLAUSSEN, H., BUNING, C., RAREY, M., AND LENQAUER, T. FlexE: Efficient molecular docking considering protein structure variations. J. Mol. Biol. 308 (2001), 377-395.
9. CONTI, E., STACHELHAUS, T., MARAHIEL, M., AND BRICK, P. Structural basis for the activation of phenylalanine in the non-ribosomal biosynthesis of Gramicidin S. EMBO J. 16 (1997), 4174-4183.
10. CORNELL, W., CIEPLAK, P., BAYLY, C., GOULD, T., MERZ, K., FERGUSON, D., SPELLMEYER, D., Fox, T., CALDWELL, J., AND KOLLMAN, P. A second generation force field for the simulation of proteins, nucleic acids and organic molecules. J. Am. Chem. Soc. 117 (1995), 5179-5197.
11. DECANNIERE, K., TRANSUE, T., DESMYTER, A., MAES, D., MUYLDERMANS, S., AND WYNS, L. Degenerate interfaces in antigen-antibody complexes. J. Mol. Biol. 313 (2001), 473-478.
12. DESMET, J., MAEYER, M., HAZES, B., AND LASTERS, I. The dead-end elimination theorem and its use in protein side-chain positioning. Nature 356 (1992), 539-542.
13. DOEKEL, S., AND MARAHIEL, M. Dipeptide formation on engineered hybrid peptide synthetases. Chem. Biol. 7 (2000), 373-384.
14. EHMANN, D., TRAUGER, J., STACHELHAUS. T., AND WALSH, C. Aminoacyl-SNACs as small-molecule substrates for the condensation domains of nonribosomal peptide synthetases. Chem. Biol. 7 (2000), 765-772.
15. EISENBERG, D., AND MCLACHLAN, A. Solvation energy in protein folding and binding. Nature 319 (1984), 199-203.
16. EPPELMANN, K., STACHELHAUS, T., AND MARAHIEL, M. Exploitation of the selectivity-conferring code of nonribosomal peptide synthetases for the rational design of novel peptide antibiotics. Biochemistry 41 (2002), 9718-9726.
17. FAUCHÈRE, J., AND PLIŠKA, V. Hydrophobic parameters II of amino-acid side chains from the partitioning of n-acetyl-amino-acid amides. Eur. J. Med. Chem. Chim. Ther. 18 (1983), 369-375.
18. HELLINGA, H., AND RICHARDS, F. Construction of new ligand binding sites in proteins of known structure: I. Computer-aided modeling of sites with pre-defined geometry. J. Mol. Biol. 222 (1991), 763-785.
19. HILL, T. Statistical Mechanics: Principles and Selected Applications. McGraw-Hill Book Company, Inc., New York., New York, 1956, ch. 1, "Principles of Classical Statistical Mechanics", pp. 1-17.
20. JARAMILLO, A., WERNISCH, L., HÉRY, S., AND WODAK, S. Automatic procedures for protein design. Comb. Chem. High Throughput Screen. 4 (2001), 643-659.
21. JIM, W., KAMBARA, O., SASAKAWA, H., TAMURA, A., AND TAKADA, S. De novo design of foldable proteins with smooth folding funnel: Automated negative design and experimental verification. Structure 11 (2003), 581-591.
22. KEATING, A., MALASHKEVICH, V., TIDOR, B., AND KIM, P. Side-chain repacking calculations for predicting structures and stabilities of heterodimeric coiled coils. Proc. Natl. Acad. Sci. USA 98 (2001), 14825-14830.
23. KNEGTEL, R., KUNTZ, I., AND OSHIRO, C. Molecular docking to ensembles of protein structures. J. Mol. Biol 266 (1997), 424-440.
24. KUNTZ, I., BLANEY, J., OATLEY, S., LANGRIDGE, R., AND FERRIN, T. A geometric approach to macromolecular-ligand interactios. J. Mol. Biol. 161 (1982), 269-288.
25. LASTERS, I., AND DESMET, J. The fuzzy-end elimination theorem: correctly implementing the side chain placement algorithm based on the dead-end elimination theorem. Protein Eng. 6 (1993), 717-722.
26. LILIEN, R., SRIDHARAN, M., HUANG, J., BUSHWELLER, J., AND DONALD, B. Computational screening studies for Core Binding Factor Beta: Use of multiple conformations to model receptor flexibility. Poster - 8th International Conference on Intelligent Systems for Molecular Biology ISMB-2000.
27. LINNE, U., DOEKEL, S., AND MARAHIEL, M. Portability of epimerization domain and role of peptidyl carrier protein on epimerization activity in nonribosomal peptide synthetases. Biochemistry 40 (2001), 15824-15834.
28. LODGER, L., DWYER, M., SMITH, J., AND HELLINGA, H. Computational design of receptor and sensor proteins with novel functions. Nature 423 (2003), 185-190.
29. LORBER, D., ANDSHOICHET, B. Flexible ligand docking using conformational ensembles. Protein Sci. 7 (1998), 938-950.
30. LOVELL, S., WORD. J., RICHARDSON, J., AND RICHARDSON, D. The penultimate rotamer library. Proteins 40 (2000), 389-408.
31. MARVIN, J., AND HELLINGA, H. Conversion of a maltose receptor into a zinc biosensor by computational design. PNAS 98 (2001), 4955-4960.
32. MCQUARRIE, D. Statistical Mechanics. Harper & Row, New York, 1976.
33. MONTFORT, W., PERRY, K., FAUMAN, E., FINER-MOORE, J., MALEY, G., HARDY, L., MALEY, F., AND STROUD, R. Structure, multiple site binding, and segmental accommodation in thymidylate synthase on binding dUMP and an anti-folate. Biochemistry 29 (1990), 6964-6977.
34. MOOTZ, H., SCHWARZER, D., AND MARAHIEL. M. Construction of hybrid peptide synthetases by module and domain fusions. Proc. Natl. Acad. Sci. USA 97 (2000), 5848-5853.
35. MURTHY, K., WINBORNE, E., MINNICH, M., CULP, J., AND DEBOUCK, C. The Crystal Structures at 2.2-Å Resolution of Hydroxyethylene-based Inhibitors Bound to Human Immunodeficiency Virus Type 1 Protease Show the Inhibitors Are Present in Two Distinct Orientations. J. Biol. Chem. 267 (1992), 22770-22778.
36. OFFREDI, F., DUBAIL, F., KISCHEL, P., SARINSKI, K., STERN, A., VAN DE WEERDT, C., HOCH, J., PROSPERI, C., FRANÇOIS, J., MAYO, S., AND MARTIAL, J. De novo backbone and sequence design of an idealized α/β-barreI protein: evidence of stable tertiary structure. J. Mol. Biol. 325 (2003), 163-174.
37. ÖSTERBERG, F., MORRIS, G., SANNER, M., OLSON, A., AND GOODSELL, D. Automated docking to multiple target structures: Incorporation of protein mobility and structural water heterogeneity in autodock. Proteins 46 (2002), 34-40.
38. PHILIPPOPOULOS, M., AND LIM, C. Exploring the dynamic information content of a protein NMR structure: Comparison of a molecular dynamics simulation with the NMR and X-Ray structures of Escherichia coli ribonuclease HI. Proteins 36 (1999). 87-110.
39. PIERCE. N., AND E., W. Protein design is W-hard. Protein Eng. 15 (2002), 779-782.
40. PIERCE, N., SPRIET, J., DESMET, J., AND MAYO, S. Conformational splitting: a more powerful criterion for dead-end elimination. J. Comput. Chem. 21 (2000), 999-1009.
41. PONDER, J., AND RICHARDS, F. Tertiary templates for proteins: use of packing criteria in the enumeration of allowed sequences for different structural classes. J. Mol. Biol. 193 (1987), 775-791.
42. RAAG, R., AND POULOS, L. Crystal structures of cytochrome P-450CAM complexed with camphane, thiocamphor, and adamantane: factors controlling P-450 substrate hydroxylation. Biochemistry 30(1991), 2674-2684.
43. RIENSTRA, C., TUCKER-KELLOGG. L., JARONIEC, C., HOHWY, M., REIF, B., MCMAHON, M., TIDOR, B., LOZANO-PÉREZ, T., AND GRIFFIN, R. De novo determination of peptide structure with solid-state magic-angle spinning NMR spectroscopy. Proc. Natl. Acad. Sci. USA 99 (2002), 10260-10265.
44. SAMANTA, U., PAL, D., AND CHAKRABARTI, P. Packing of aromatic rings against tryptophan residues in proteins. Acta Cryst. D 55 (1999), 1421-1427.
45. SCHNEIDER, A., STACHELHAUS. T., AND MARAHIEL. M. Targeted alteration of the substrate specificity of peptide synthetases by rational module swapping. Mol. Gen. Genet. 257 (1998), 308-318.
46. SCHWARZER, D., FJNKING, R., AND MARAHIEL, M. Nonribosomal peptides: from genes to products. Nat. Prod. Rep. 20 (2003), 275-287.
47. SHIFMAN, J., AND MAYO, S. Modulating calmodulin binding specificity through computational protein design. J. Mol. Biol. 323 (2002), 417-423.
48. STACHELHAUS, T., AND MARAHIEL, M. Modular structure of peptide synthetases revealed by dissection of the multifunctional enzyme GrsA. J. Biol. Chem. 270 (1995), 6163-6169.
49. STACHELHAUS, T., MOOTZ, H., AND MARAHIEL, M. The speciflciy-conferring code of adenylation domains in nonribosomal peptide synthetases. Chem. Biol. 6 (1999), 493-505.
50. STACHELHAUS, T., SCHNEIDER, A., AND MARAHIEL, M. Rational design of peptide antibiotics by targeted replacement of bacterial and fungal domains. Science 269 (1995), 69-72.
51. STREET, A., AND MAYO, S. Computational protein design. Structure 7 (1999), R105-R109.
52. TUCKER-KELLOGG, L. Systematic Conformational Search with Constraint Satisfaction. PhD thesis, Massachusetts Institute of Technology, 2002.
53. WEBER. T., BAUMGARTNER, R., RENNER, C., MARAHIEL, M., AND HOLAK, T. Solution structure of PCP, a prototype for the peptidyl carrier domains of modular peptide synthetases. Structure 8 (2000), 407-418.
54. WEINER, S., KOLLMAN, P., CASE. D., SINGH, U., GHIO, C., ALAGONA, G., PROFETA, S., AND WEINER, P. A new force field for molecular mechanical simulation of nucleic acids and proteins. J. Am. Chem. Soc. 106 (1984), 765-784.
55. WOJTCZAK, J., CODY, V., LUFT, J., AND PANOBORN, W. Structures of human transthyretin complexed with thyroxine at 2.0Å resolution and 3′, 5′-Dinitro-N-acetyl-L-thyronine at 2.2Å resolution. Acta Cryst. D 52 (1996), 758-765.
56. ZHOU, G., FERRER, M., CHOPRA, R., KAPOOR. T., STRASS-MAIER, T., WEISSENHORN, W., SKEHEL, J., OPRIAN, D., SCHREIBER, S., HARRISON, S., AND WILEY, D. The structure of an HIV-1 specific cell entry inhibitor in complex with the HIV-1 gp41 trimeric core. Bioorg. Med. Chem. 8 (2000), 2219-2228.