De Novo Protein Design: Fully Automated Sequence Selection
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 × 10$^{27}$ possible a...
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| Veröffentlicht in: | Science (American Association for the Advancement of Science) 1997-10, Vol.278 (5335), p.82-87 |
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| creator | Dahiyat, Bassil I. Mayo, Stephen L. |
| description | 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 × 10$^{27}$ possible amino acid sequences for compatibility with the design target, a ββα 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. |
| doi_str_mv | 10.1126/science.278.5335.82 |
| format | Article |
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A computational design algorithm based on physical chemical potential functions and stereochemical constraints was used to screen a combinatorial library of 1.9 × 10$^{27}$ possible amino acid sequences for compatibility with the design target, a ββα 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. 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Psychology ; Hydrogen Bonding ; Hydrogen bonds ; Inhalants ; Libraries ; Literary Devices ; Magnetic Resonance Spectroscopy ; Mathematical sequences ; Mathematics ; Methods. Procedures. Technologies ; Models, Molecular ; Molecular Sequence Data ; Organic Chemistry ; Protein biosynthesis ; Protein Conformation ; Protein Engineering ; Protein Folding ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Protein synthesis ; Proteins ; Protons ; Research Article ; Scientific Concepts ; Scoring ; Sequence Alignment ; Solutions ; Solvents ; Synthesis ; Transcription Factors - chemical synthesis ; Transcription Factors - chemistry ; Zinc ; Zinc Fingers</subject><ispartof>Science (American Association for the Advancement of Science), 1997-10, Vol.278 (5335), p.82-87</ispartof><rights>Copyright 1997 American Association for the Advancement of Science</rights><rights>1997 INIST-CNRS</rights><rights>COPYRIGHT 1997 American Association for the Advancement of Science</rights><rights>COPYRIGHT 1997 American Association for the Advancement of Science</rights><rights>Copyright American Association for the Advancement of Science Oct 3, 1997</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c779t-2c48c232d073e657023102d131cb1bcea30dd35328a13251799e4bc114ea55713</citedby><cites>FETCH-LOGICAL-c779t-2c48c232d073e657023102d131cb1bcea30dd35328a13251799e4bc114ea55713</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/2894510$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/2894510$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>314,780,784,803,2884,2885,27924,27925,58017,58250</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=2851150$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9311930$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Dahiyat, Bassil I.</creatorcontrib><creatorcontrib>Mayo, Stephen L.</creatorcontrib><title>De Novo Protein Design: Fully Automated Sequence Selection</title><title>Science (American Association for the Advancement of Science)</title><addtitle>Science</addtitle><description>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 × 10$^{27}$ possible amino acid sequences for compatibility with the design target, a ββα 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.</description><subject>Algorithms</subject><subject>Amino Acid Sequence</subject><subject>Amino acids</subject><subject>Atomic structure</subject><subject>Atoms</subject><subject>Automation</subject><subject>Biological and medical sciences</subject><subject>Biotechnology</subject><subject>Chemical bonds</subject><subject>Chemistry</subject><subject>Computer Simulation</subject><subject>Coordinate systems</subject><subject>Crystallography, X-Ray</subject><subject>Design</subject><subject>DNA-Binding Proteins - chemical synthesis</subject><subject>DNA-Binding Proteins - chemistry</subject><subject>Fundamental and applied biological sciences. 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A computational design algorithm based on physical chemical potential functions and stereochemical constraints was used to screen a combinatorial library of 1.9 × 10$^{27}$ possible amino acid sequences for compatibility with the design target, a ββα 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.</abstract><cop>Washington, DC</cop><pub>American Society for the Advancement of Science</pub><pmid>9311930</pmid><doi>10.1126/science.278.5335.82</doi><tpages>6</tpages></addata></record> |
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| identifier | ISSN: 0036-8075 |
| ispartof | Science (American Association for the Advancement of Science), 1997-10, Vol.278 (5335), p.82-87 |
| issn | 0036-8075 1095-9203 |
| language | eng |
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| source | MEDLINE; JSTOR Archive Collection A-Z Listing; American Association for the Advancement of Science |
| subjects | Algorithms Amino Acid Sequence Amino acids Atomic structure Atoms Automation Biological and medical sciences Biotechnology Chemical bonds Chemistry Computer Simulation Coordinate systems Crystallography, X-Ray Design DNA-Binding Proteins - chemical synthesis DNA-Binding Proteins - chemistry Fundamental and applied biological sciences. Psychology Hydrogen Bonding Hydrogen bonds Inhalants Libraries Literary Devices Magnetic Resonance Spectroscopy Mathematical sequences Mathematics Methods. Procedures. Technologies Models, Molecular Molecular Sequence Data Organic Chemistry Protein biosynthesis Protein Conformation Protein Engineering Protein Folding Protein Structure, Secondary Protein Structure, Tertiary Protein synthesis Proteins Protons Research Article Scientific Concepts Scoring Sequence Alignment Solutions Solvents Synthesis Transcription Factors - chemical synthesis Transcription Factors - chemistry Zinc Zinc Fingers |
| title | De Novo Protein Design: Fully Automated Sequence Selection |
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