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Biology

Protein visdom; Workbench for Published: July 25, 2013 doi: 10.3791/50476
Automatic Translation
1, 1, 1, 1, 1
1Department of Chemical and Biological Engineering, Princeton University

Abstract

Målet med de novo protein design er å finne de aminosyresekvensene som vil foldes sammen til en ønsket 3-dimensjonal struktur og forbedringen i bestemte egenskaper, for eksempel bindingsaffinitet, agonist eller antagonist oppførsel, eller stabilitet, i forhold til den opprinnelige sekvens. Protein utforming ligger i sentrum av strøm fremskritt drug design og oppdagelse. Ikke bare gir protein utforming spådommer for potensielt nyttige narkotika mål, men også forbedrer vår forståelse av protein folding prosessen og protein-protein interaksjoner. Eksperimentelle metoder som anvist utvikling viser suksess i protein utforming. Men slike metoder begrenset av den begrensede sekvens plass som kan søkes tractably. I kontrast,-bearbeiding design strategier tillate for screening av et mye større sett med sekvenser som dekker et bredt spekter av egenskaper og funksjonalitet. Vi har utviklet en rekke beregningsorientert de novo protein utforming methods i stand til å takle flere viktige områder av protein design. Disse inkluderer utformingen av monomere proteiner for økt stabilitet og komplekser for økt bindingsaffinitet.

Å spre disse metodene for bredere bruker vi presentere Protein WISDOM ( http://www.proteinwisdom.org ), et verktøy som gir automatiserte metoder for en rekke protein design problemer. Strukturelle maler er presentert for å initialisere designprosessen. Den første fasen av design er en optimalisering sekvens utvalg scenen som tar sikte på å bedre stabilitet gjennom minimering av potensielle energien i sekvensen plass. Valgte sekvensene blir deretter kjørt gjennom en fold spesifisitet scene og en bindende affinitet scenen. En rang sortert liste av sekvensene for hvert trinn i prosessen, sammen med relevante designet strukturer, gir brukeren en omfattende kvantitativ vurdering av design. Her gir vi detaljene of hver design metode, så vel som flere kjente eksperimentelle suksesser oppnådd gjennom bruk av metodene.

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Protein visdom; Workbench for<em&gt; I silikon</em&gt;<em&gt; De novo</em&gt; Design av biomolekyler
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Smadbeck, J., Peterson, M. B.,… More

Smadbeck, J., Peterson, M. B., Khoury, G. A., Taylor, M. S., Floudas, C. A. Protein WISDOM: A Workbench for In silico De novo Design of BioMolecules. J. Vis. Exp. (77), e50476, doi:10.3791/50476 (2013).

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