Protein design is the engineering of natural amino acid sequences to modify and/or create desired protein structures or functions.
Keywords: protein; inverse folding; sequence sampling; automated design; molecular evolution
Emmanuel Lacroix, European Molecular Biology Laboratory, Heidelberg, Germany
Luis Serrano, European Molecular Biology Laboratory, Heidelberg, Germany
Published online: April 2001
DOI: 10.1038/npg.els.0003034
Protein design is the engineering of natural amino acid sequences to modify and/or create desired protein structures or functions.
Keywords: protein; inverse folding; sequence sampling; automated design; molecular evolution
| References | |
| Altamirano MM, Blackburn JM, Aguayo C and Fersht AR (2000) Directed evolution of new catalytic activity using the alpha/beta-barrel scaffold. Nature 403: 617622. | |
| Dahiyat BI and Mayo SL (1996) Protein design automation. Protein Science 5(5): 895903. | |
| Dahiyat BI and Mayo SL (1997) De novo protein design: fully automated sequence selection. Science 278: 8287. | |
| Dahiyat BI, Gordon DB and Mayo SL (1997) Automated design of the surface positions of protein helices. Protein Science 6: 13331337. | |
| Desjarlais JR and Handel TM (1995) De novo design of the hydrophobic cores of proteins. Protein Science 4: 20062018. | |
| Domingues H, Cregut D, Sebald W, Oschkinat H and Serrano L (1999) Rational design of a GCN4-derived mimetic of interleukin-4. Nature Structural Biology 6: 652656. | |
| Godzik A (1995) In search of the ideal protein sequence. Protein Engineering 8: 409416. | |
| Hecht MH, Richardson JS, Richardson DC and Ogden RC (1990) De novo design, expression, and characterization of Felix: a four-helix bundle protein of native-like sequence. Science 249: 884891. | |
| Hurley JH, Baase WA and Matthews BW (1992) Design and structural analysis of alternative hydrophobic core packing arrangements in bacteriophage T4 lysozyme. Journal of Molecular Biology 224: 11431159. | |
| Jones DT (1994) De novo protein design using pairwise potentials and a genetic algorithm. Protein Science 3: 567574. | |
| Joo H, Lin Z and Arnold FH (1999) Laboratory evolution of peroxide-mediated cytochrome P450 hydroxylation. Nature 399: 670673. | |
| Kamtekar S, Schiffer JM, Xiong H, Babik JM and Hecht MH (1993) Protein design by binary patterning of polar and nonpolar amino acids. Science 262: 16801685. | |
| Lazar GA, Desjarlais JR and Handel TM (1997) De novo design of the hydrophobic core of ubiquitin. Protein Science 6: 11671178. | |
| Pabo C (1983) Molecular technology. Designing proteins and peptides. Nature 301: 200. | |
| Regan L and DeGrado WF (1988) Characterization of a helical protein designed from first principles. Science 241: 976978. | |
| Riddle DS, Santiago JV, Bray-Hall ST et al. (1997) Functional rapidly folding proteins from simplified amino acid sequences. Nature Structural Biology 4: 805809. | |
| Further Reading | |
| DeGrado WF, Wasserman ZR and Lear JD (1989) Protein design, a minimalist approach. Science 243: 622628. | |
| DeGrado WF, Summa CM, Pavone V, Nastri F and Lombardi A (1999) De novo design and structural characterization of proteins and metalloproteins. Annual Review of Biochemistry 68: 779819. | |
| Desjarlais JR and Clarke ND (1998) Computer search algorithms in protein modification and design. Current Opinion in Structural Biology 8: 471475. | |
| Gordon DB, Marshall SA and Mayo SL (1999) Energy functions for protein design. Current Opinion in Structural Biology 9: 509513. | |
| Lacroix E and Serrano L (2000) The EMBL Protein Design Unit. [http://ProteinDesign.EMBL-Heidelberg.DE] | |
| Petrounia IP and Arnold FH (2000) Designed evolution of enzymatic properties. Current Opinion in Biotechnology 11: 325330. | |
| Street AG and Mayo SL (1999) Computational protein design. Structure with Folding and Design 7: R105109. | |