Latest
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Computational design of an enzyme catalyst for a stereoselective bimolecular Diels-Alder reaction
Siegel and Zanghellini et al, Science, 329, 309-313. (2010) Structure of a designed Diels-Alderase. (A) Surface view of the design model (DA_20_00, green) bound to the substrates (diene and dienophile, purple). The catalytic residues making the designed hydrogen bonds are depicted as sticks. (B) Overlay of the design model (DA_20_00,brown) and crystal structure of DA_20_00_A74I (green). The crystal…
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Structure prediction problems solved by Foldit players
Cooper, Khatib et al, Nature, 466, 756-60. (2010) Examples of blind structure prediction problems in which players were successfully able to improve structures. Native structures are shown in blue, starting puzzles in red, and top scoring Foldit predictions in green. (a) The red starting puzzle had a register shift and the top scoring green Foldit prediction…
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Exploitation of binding energy for catalysis and design
Thyme, Summer B., et all. Nature 461, 1300-4. (2009) The monomeric homing endonuclease I-AniI cleaves with high sequence specificity in the center of a 20 base-pair DNA target site, with the N-terminal domain of the enzyme making extensive binding interactions with the left (-) side of the target site and the similarly structured C-terminal domain…
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De novo computational design of retro-aldol enzymes
Jiang, Lin, Althoff Eric A. et al, Science, 319, 1387-91. (2008) Using new algorithms that employ hashing techniques to construct active sites for multi-step reactions, we designed retro-aldolases that employ four different catalytic motifs to catalyze the breaking of a carbon-carbon bond in a non-natural substrate. Designs that utilized an explicit water molecule to mediate…
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High Resolution Protein Structure Refinement
Qian B, Raman S, et al. Nature 450, 259-64. (2007) A longstanding problem in computational biology is the refinement of low resolution protein structure models to more atomic-level accurate structures. A related challenge is refining low-resolution NMR models to the quality of high-resolution structures. NMR is a valuable tool for determining protein structures, particularly because…
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Computational Design of Protein-DNA Cleavage Specificity in a Homing Endonuclease
Ashworth J, Havranek JJ, et al. Nature 441, 656-9. (2006) High-resolution modeling of protein-DNA interactions has granted us the ability to estimate the specificities of real and hypothetical interfaces. This approach may be useful to design novel sequence-specific endonucleases for biotechnology and medicine. The figure at left depicts the (crystallographically and biochemically validated) model of…
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Design of a novel globular protein fold with atomic level accuracy
Kuhlman B, Dantas G, et al. Science 302, 1364-8. (2003) A major challenge of computational protein design is the creation of novel proteins with arbitrarily chosen three-dimensional structures. Here, we used a general computional strategy that iterates between sequence design and structure prediction to design a 93-residue alpha/beta protein called Top7 with a novel sequence…
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Blind ab initio structure prediction of CASP3 targets
Simons, K.T., Bonneau, et al. Proteins 3, 171-176 (1999) To generate structures consistent with both the local and non-local interactions responsible for protein stability, 3 and 9 residue fragments of known structures with local sequences similar to the target sequence were assembled into complete tertiary structures using a Monte Carlo simulated annealing procedure (Simons, K.T.…