Abstract
Computational methods continue to facilitate efforts in protein design. Most of this work has focused on searching sequence space to identify one or a few sequences compatible with a given structure and functionality. Probabilistic computational methods provide information regarding the range of amino acid variability permitted by desired functional and structural constraints. Such methods may be used to guide the construction of both individual sequences and combinatorial libraries of proteins.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Go, N. (1983) Theoretical studies of protein folding. Annu. Rev. Biophys. Bioeng. 12, 183–210.
Shea, J. E. and Brooks, C. L. 3rd. (2001) From folding theories to folding proteins: a review and assessment of simulation studies of protein folding and unfolding. Annu. Rev. Phys. Chem. 52, 499–535.
Brooks, C. L. 3rd. (2002) Protein and peptide folding explored with molecular simulations. Acc. Chem. Res. 35, 447–454.
Kraemer-Pecore, C. M., Wollacott, A. M., and Desjarlais, J. R. (2001) Computational protein design. Curr. Opin. Chem. Biol. 5, 690–695.
Bryson, J. W., Betz, S. F., Lu, H. S., et al. (1995) Protein design: a hierarchic approach. Science 270, 935–941.
Dunbrack, R. (2002) Rotamer libraries. Curr. Opin. Struct. Biol. 12, 431–440.
Shakhnovich, E. I. and Gutin, A. M. (1993) A new approach to the design of stable proteins. Protein Eng. 6, 793–800.
Jones, D. T. (1994) De novo protein design using pairwise potentials and a genetic algorithm. Protein Sci. 3, 567–574.
Hellinga, H. W. and Richards, F. M. (1994) Optimal sequence selection in proteins of known structure by simulated evolution. Proc. Natl. Acad. Sci. USA 91, 5803–5807.
Desjarlais, J. R. and Handel, T. M. (1995) De-novo design of the hydrophobic cores of proteins. Protein Sci. 4, 2006–2018.
Johnson, E. C., Lazar, G. A., Desjarlais, J. R., and Handel, T. M. (1999) Solution structure and dynamics of a designed hydrophobic core variant of ubiquitin. Struct. Fold. Des. 7, 967–976.
Jiang, X., Farid, H., Pistor, E., and Farid, R. S. (2000) A new approach to the design of uniquely folded thermally stable proteins. Protein Sci. 9, 403–416.
Jiang, X., Bishop, E. J., and Farid, R. S. (1997) A de novo designed protein with properties that characterize natural hyperthermophilic proteins. J. Am. Chem. Soc. 119, 838, 839.
Bryson, J. W., Desjarlais, J. R., Handel, T. M., and DeGrado, W. F. (1998) From coiled coils to small globular proteins: design of a native-like three-helix bundle. Protein Sci. 7, 1404–1414.
Walsh, S. T. R., Cheng, H., Bryson, J. W., Roder, H., and DeGrado, W. F. (1999) Solution structure and dynamics of a denovo designed three-helix bundle protein. Proc. Natl. Acad. Sci. USA 96, 5486–5491.
Voigt, C. A., Gordon, D. B., and Mayo, S. L. (2000) Trading accuracy for speed: a quantitative comparison of search algorithms in protein sequence design. J. Mol. Biol. 299, 789–803.
Gordon, D. B. and Mayo, S. L. (1998) Radical performance enhancements for combinatorial optimization algorithms based on the dead-end elimination theorem. J. Comput. Chem. 19, 1505–1514.
Gordon, D. B. and Mayo, S. L. (1999) Branch-and terminate: a combinatorial optimization algorithm for protein design. Struct. Fold. Des. 7, 1089–1098.
Pierce, N. A., Spriet, J. A., Desmet, J., and Mayo, S. L. (2000) Conformational splitting: a more powerful criterion for dead-end elimination. J. Comput. Chem. 21, 999–1009.
Looger, L. L. and Hellinga, H. W. (2001) Generalized dead-end elimination algorithms make large-scale protein side-chain structure prediction tractable: implications for protein design and structural genomics. J. Mol. Biol. 307, 429–445.
Dahiyat, B. I. and Mayo, S. L. (1997) De novo protein design: fully automated sequence selection. Science 278, 82–87.
Marshall, S. A. and Mayo, S. L. (2001) Achieving stability and conformational specificity in designed proteins via binary patterning. J. Mol. Biol. 305, 619–631.
Malakauskas, S. M. and Mayo, S. L. (1998) Design, structure, and stability of a hyperthermophilic protein variant. Nat. Struct. Biol. 5, 470–475.
Strop, P. and Mayo, S. L. (1999) Rubredoxin variant folds without iron. J. Am. Chem. Soc. 121, 2341–2345.
Shimaoka, M., Shifman, J. M., Jing, H., Takagi, L., Mayo, S. L., and Springer, T. A. (2000) Computational design of an integrin i domain stabilized in the open high affinity conformation. Nat. Struct. Biol. 7, 674–678.
Benson, D. E., Wisz, M. S., Liu, W., and Hellinga, H. W. (1998) Construction of a novel redox protein by rational design: conversion of a disulfide bridge into a mononuclear iron-sulfur center. Biochemistry 37, 7070–7076.
DeGrado, W. F., Summa, C. M., Pavone, V., Nastri, F., and Lombardi, A. (1999) De novo design and structural characterization of proteins and metalloproteins. Annu. Rev. Biochem. 68, 779–819.
Bolon, D. N. and Mayo, S. L. (2001) Enzyme-like proteins by computational design. Proc. Natl. Acad. Sci. USA 98, 14,274–14,279.
Street, A. G. and Mayo, S. L. (1999) Computational protein design. Struct. Fold. Des. 7, R105–R109.
Saven, J. G. (2001) Designing protein energy landscapes. Chem. Rev. 101, 3113–3130.
Gromiha, M. M., Uedaira, H., An, J., Selvaraj, S., Prabakaran, P., and Sarai, A. (2002) Protherm, thermodynamic database for proteins and mutants: developments in version 3.0. Nucleic Acids Res. 30, 301, 302.
Calhoun, J. R., Kono, H., Lahr, S., Wang, W., DeGrado, W. F., and Saven, J. G. (2003) Computational design and characterization of a monomeric helical dinuclear metalloprotein. J. Mol. Biol. 334, 1101–1115.
Slovic, A. M., Kono, H., Lear, J. D., Saven, J. G., and DeGrado, W. F. (2004) Computational design of water-soluble analogues of the potassium channel kcsa. Proc. Natl. Acad. Sci. USA 101, 1828–1833.
Zou, J. and Saven, J. G. (2003) Using self-consistent fields to bias monte carlo methods with applications to designing and sampling protein sequences. J. Chem. Phys. 118, 3843–3854.
Park, S., Kono, H., Wang, W., Boder, E. T., and Saven, J. G. (2005) Progress in the development and application of computational methods for probabilistic protein design. Comp. Chem. Eng. 24, 407–421.
Keefe, A. D. and Szostak, J. W. (2001) Functional proteins from a random-sequence library. Nature 410, 715–718.
Rojas, N. R. L., Kamtekar, S., Simons, C. T., et al. (1997) De novo heme proteins from designed combinatorial libraries. Protein Sci. 6, 2512–2524.
Roy, S., Ratnaswamy, G., Boice, J. A., Fairman, R., McLendon, G., and Hecht, M. H. (1997) A protein designed by binary patterning of polar and nonpolar amino acids displays native-like properties. J. Am. Chem. Soc. 119, 5302–5306.
Roy, S., Helmer, K. J., and Hecht, M. H. (1997) Detecting native-like properties in combinatorial libraries of de novo proteins. Fold. Des. 2, 89–92.
Finucane, M. D., Tuna, M., Lees, J. H., and Woolfson, D. N. (1999) Core-directed protein design. I. An experimental method for selecting stable proteins from combinatorial libraries. Biochemistry 38, 11,604, 11,612.
Xu, G. F., Wang, W. X., Groves, J. T., and Hecht, M. H. (2001) Self-assembled monolayers from a designed combinatorial library of de novo beta-sheet proteins. Proc. Natl. Acad. Sci. USA 98, 3652–3657.
Case, M. A. and McLendon, G. L. (2000) A virtual library approach to investigate protein folding and internal packing. J. Am. Chem. Soc. 122, 8089, 8090.
Arndt, K. M., Pelletier, J. N., Müller, K. M., Alber, T., Michnick, S. W., and Plückthun, A. (2000) A heterodimeric coiled-coil peptide pair selected in vivo from a designed library-versus-library ensemble. J. Mol. Biol. 295, 627–639.
Zhao, H. M. and Arnold, F. H. (1997) Combinatorial protein design: strategies for screening protein libraries. Curr. Opin. Struct. Biol. 7, 480–485.
Giver, L. and Arnold, F. H. (1998) Combinatorial protein design by in vitro recombination. Curr. Opin. Chem. Biol. 2, 335–338.
Hoess, R. H. (2001) Protein design and phage display. Chem. Rev. 101, 3205–3218.
Moffet, D. A. and Hecht, M. H. (2001) De novo proteins from combinatorial libraries. Chem. Rev. 101, 3191–3203.
Holm, L. and Sander, C. (1998) Touring protein fold space with dali/fssp. Nucleic Acids Res. 26, 316–319.
Luthy, R., Bowie, J. U., and Eisenberg, D. (1992) Assessment of protein models with 3-dimensional profiles. Nature 356, 83–85.
Durbin, R., Eddy, S., Krogh, A., and Mitchison, G. (1998) Biological Sequence Analysis: Probabilistic Models of Proteins and Nucleic Acids. Cambridge University Press, Cambridge, UK.
Raha, K., Wollacott, A. M., Italia, M. J., and Desjarlais, J. R. (2000) Prediction of amino acid sequence from structure. Protein Sci. 9, 1106–1119.
Kuhlman, B. and Baker, D. (2000) Native protein sequences are close to optimal for their structures. Proc. Natl. Acad. Sci. USA 97, 10,383–10,388.
Koehl, P. L. M. (1999) De novo protein design. I. In search of stability and specificity. J. Mol. Biol. 239, 1161–1181.
Koehl, P. L. M. (1999) De novo protein design. II. Plasticity in sequence space. J. Mol. Biol. 293, 1183–1193.
Kraemer-Pecore, C. M., Lecomte, J. T., and Desjarlais, J. R. (2003) A de novo redesign of the ww domain. Protein Sci. 12, 2194–2205.
Larson, S. M., England, J. L., Desjarlais, J. R., and Pande, V. S. (2002) Thoroughly sampling sequence space: large-scale protein design of structural ensembles. Protein Sci. 11, 2804–2813.
Hayes, R. J., Bentzien, J., Ary, M. L., Hwang, M. Y., Jacinto, J. M., Vielmetter, J., Kundu, A., and Dahiyat, B. I. (2002) Combining computational and experimental screening for rapid optimization of protein properties. Proc. Natl. Acad. Sci. USA 99, 15,926–15,931.
Zou, J. and Saven, J. G. (2000) Statistical theory of combinatorial libraries of folding proteins: energetic discrimination of a target structure. J. Mol. Biol. 296, 281–294.
Kono, H. and Saven, J. G. (2001) Statistical theory for protein combinatorial libraries. Packing interactions, backbone flexibility, and the sequence variability of a main-chain structure. J. Mol. Biol. 306, 607–628.
Dunbrack, R. and Cohen, F. E. (1997) Bayesian statistical analysis of protein side-chain retainer preferences. Protein Sci. 6, 1661–1681.
McQuarrie, D. A. (1976) Statistical mechanics. Harper and Row, New York.
Press, W. H., Teukolsky, S. A., Vetterling, W. T., and Flannery, B. P. (1992) Numerical recipes. 2nd ed., Cambridge University Press, Cambridge, UK.
Weiner, S. J., Kollman, P. A., Case, D. A., et al. (1984) A new force field for molecular mechanical simulation of nucleic acids and proteins. J. Am. Chem. Soc. 106, 765–784.
Kono, H. and Doi, J. (1996) A new method for side-chain conformation prediction using a hopfield network and reproduced rotamers. J. Comput. Chem. 17, 1667–1683.
Wernisch, L., Hery, S., and Wodak, S. J. (2000) Automatic protein design with all atom force-fields by exact and heuristic optimization. J. Mol. Biol. 301, 713–736.
Sander, C. and Schneider, R. (1991) Database of homology-derived protein structures and the structural meaning of sequence alignment. Proteins 9, 56–68.
Jensen, L. J., Andersen, K. V., Svendsen, A., and Kretzschmar, T. (1998) Scoring functions for computational algorithms applicable to the design of spiked oligonucleotides. Nucleic Acids Res. 26, 697–702.
Wolf, E. and Kim, P. S. (1999) Combinatorial codons: a computer program to approximate amino acid probabilities with biased nucleotide usage. Protein Sci. 8, 680–688.
Wang, W. and Saven, J. G. (2002) Designing gene libraries from protein profiles for combinatorial protein experiments. Nucleic Acids Res. 30, e120.
Eriksson, A. E., Baase, W. A., Zhang, X. J., Heinz, D. W., Blaber, M., Baldwin, E. P., and Matthews, B. W. (1992) Response of a protein structure to cavity-creating mutations and its relation to the hydrophobic effect. Science 255, 178–183.
Axe, D. D., Foster, N. W., and Fersht, A. R. (1996) Active barnase variants with completely random hydrophobic cores. Proc. Natl. Acad. Sci. USA 93, 5590–5594.
Voigt, C. A., Mayo, S. L., Arnold, F. H., and Wang, Z. G. (2001) Computational method to reduce the search space for directed protein evolution. Proc. Natl. Acad. Sci. USA 98, 3778–3783.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2007 Humana Press Inc.
About this protocol
Cite this protocol
Kono, H., Wang, W., Saven, J.G. (2007). Combinatorial Protein Design Strategies Using Computational Methods. In: Arndt, K.M., Müller, K.M. (eds) Protein Engineering Protocols. Methods in Molecular Biology™, vol 352. Humana Press. https://doi.org/10.1385/1-59745-187-8:3
Download citation
DOI: https://doi.org/10.1385/1-59745-187-8:3
Publisher Name: Humana Press
Print ISBN: 978-1-58829-072-4
Online ISBN: 978-1-59745-187-1
eBook Packages: Springer Protocols