Design of a Novel Globular Protein Fold with Atomic-Level Accuracy

  title={Design of a Novel Globular Protein Fold with Atomic-Level Accuracy},
  author={Brian Kuhlman and Gautam Dantas and Gregory C. Ireton and Gabriele Varani and Barry L. Stoddard and David Baker},
  pages={1364 - 1368}
A major challenge of computational protein design is the creation of novel proteins with arbitrarily chosen three-dimensional structures. Here, we used a general computational strategy that iterates between sequence design and structure prediction to design a 93-residue α/β protein called Top7 with a novel sequence and topology. Top7 was found experimentally to be folded and extremely stable, and the x-ray crystal structure of Top7 is similar (root mean square deviation equals 1.2 angstroms) to… 

Computer-based design of novel protein structures.

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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, and a BLAST search shows that the designed sequence, full sequence design 1 (FSD-1), has very low identity to any known protein sequence.

Accurate computer-based design of a new backbone conformation in the second turn of protein L.

The rational design of loops and turns is a key step towards creating proteins with new functions and in contrast to wild-type protein L the second beta-turn appears to be formed at the rate limiting step in folding.

High-resolution protein design with backbone freedom.

The de novo design of a family of alpha-helical bundle proteins with a right-handed superhelical twist is described, where the overall protein fold was specified by hydrophobic-polar residue patterning, whereas the bundle oligomerization state, detailed main-chain conformation, and interior side-chain rotamers were engineered by computational enumerations of packing in alternate backbone structures.

Prediction of amino acid sequence from structure

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De novo protein design. I. In search of stability and specificity.

A fully automated protein design strategy that works on the entire sequence of the protein and uses a full atom representation, and it is shown that each additional term of the energy function improves the performance of the design procedure.

Thoroughly sampling sequence space: Large‐scale protein design of structural ensembles

The results of a broad exploration of sequence space, with backbone flexibility, through a novel approach: large‐scale protein design to structural ensembles suggest that the diversity of designed sequences is primarily determined by a structure's overall fold, and that the designability principle postulated from studies of simple models holds in real proteins.

Coupling backbone flexibility and amino acid sequence selection in protein design

  • A. SuS. L. Mayo
  • Physics
    Protein science : a publication of the Protein Society
  • 1997
This result demonstrates that backbone flexibility can be combined explicitly with amino acid side‐chain selection and that the selection algorithm is sufficiently robust to tolerate perturbations as large as 15% of Gβ1's native supersecondary structure parameter values.