| | |  | | | | Record from Web of Science® | | | | | | |
| De novo protein design: Fully automated sequence selection |
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| Author(s): Dahiyat BI, Mayo SL |
| Source: SCIENCE Volume: 278 Issue: 5335 Pages: 82-87 Published: OCT 3 1997 |
| Times Cited: 517 References: 51 |
| Abstract: The first fully automated design and experimental validation of a novel sequence for an entire protein is described. A computational design algorithm based on physical chemical potential functions and stereochemical constraints was used to screen a combinatorial library of 1.9 x 10(27) possible amino acid sequences for compatibility with the design target, a beta beta alpha protein motif based on the polypeptide backbone structure of a zinc finger domain. A BLAST search shows that the designed sequence, full sequence design 1 (FSD-1), has very low identity to any known protein sequence. The solution structure of FSD-1 was solved by nuclear magnetic resonance spectroscopy and indicates that FSD-1 forms a compact well-ordered structure, which is in excellent agreement with the design target structure, This result demonstrates that computational methods can perform the immense combinatorial search required for protein design, and it suggests that an unbiased and quantitative algorithm can be used in various structural contexts. |
| Document Type: Article |
| Language: English |
Addresses:
1. CALTECH, HOWARD HUGHES MED INST, PASADENA, CA 91125 USA
2. CALTECH, DIV BIOL, PASADENA, CA 91125 USA
3. CALTECH, DIV CHEM & CHEM ENGN, PASADENA, CA 91125 USA |
| Publisher: AMER ASSOC ADVANCEMENT SCIENCE, 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 |
| Subject Category: Multidisciplinary Sciences |
| IDS Number: XZ124 |
| ISSN: 0036-8075 |
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| | | | | | | | | Record from Web of Science® | | | | | | | | | |