β-sheet proteins carry out critical functions in biology, and hence are attractive scaffolds for computational protein design. Despite this potential, de novo design of all-β-sheet proteins from first principles lags far behind the design of all-α or mixed-αβ domains owing to their non-local nature and the tendency of exposed β-strand edges to aggregate. Through study of loops connecting unpaired β-strands (β-arches), we have identified a series of structural relationships between loop geometry, side chain directionality and β-strand length that arise from hydrogen bonding and packing constraints on regular β-sheet structures. We use these rules to de novo design jellyroll structures with double-stranded β-helices formed by eight antiparallel β-strands. The nuclear magnetic resonance structure of a hyperthermostable design closely matched the computational model, demonstrating accurate control over the β-sheet structure and loop geometry. Our results open the door to the design of a broad range of non-local β-sheet protein structures.

• MeSH
• konformace proteinů, beta-řetězec MeSH
• konformace proteinů MeSH
• molekulární modely MeSH
• nukleární magnetická rezonance biomolekulární MeSH
• počítačová simulace MeSH
• proteinové inženýrství metody   MeSH
• proteiny chemie   genetika   MeSH
• sbalování proteinů MeSH
• sekvence aminokyselin MeSH
• stabilita proteinů MeSH
• vodíková vazba MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH