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Protein Structure Prediction
and Refinement
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If the models are good enough to predict peptide structure.
Protein Structure Refinement
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Why Refinement of Protein Structural Models.
Homology models contain little additional information compared to the template structures (unless they can be refined). An inability to determine the relative merit of ab-initio models. Bi-annual CASP competition CASP: Critical Assessment of techniques for protein Structure Prediction Aim: To refine models from ROSETTA1 (currently the best semi ab inito structure prediction algorithm.) 1. Baker et al. J. Mol. Biol. (2001) 306,
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Test-set: 20 proteins used by Baker et al. to test ROSETTA
Refinement of Protein Structural Models Test-set: 20 proteins used by Baker et al. to test ROSETTA (J. Mol. Biol. (2001) 306, ). For each protein 4 ROSETTA models released from ROSETTA The best (closest to experimental structure) The worst (furthest from experimental structure) 3. Random example 4. Random example Proceedure: Build side-chains Simulate in explicit solvent Compare to the experimental structure (do we do better or worse). Controls: Simulate experimental structure (NMR or x-ray). Simulate experimental structure with side-chains deleted and rebuilt.
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MD refinement of the best Rosetta model for 1AIF
(mercury detoxification protein) Refinement MD 100 ns NMR structure ROSETTA model 0.26 nm RMSD 0.16 nm RMSD Fan Hao
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MD Refinement of Rosetta models for 1AIF
Refinement is systematic given an ability to simulate on a relevant time scale. Fan Hao
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ROSETTA models after 5ns MD 2 NMR structure 3 1AIF 4
1.03 nm RMSD 0.90 nm RMSD 3 0.92 nm RMSD 1AIF 0.91 nm RMSD 4 Some improvement in 3 of 4 cases 0.90 nm RMSD 0.63 nm RMSD Fan Hao
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MD refinement of an alternate ROSETTA model for 1afi
MD 5 ns Refinement MD 400 ns ROSETTA model NMR structure 0.87 nm RMSD 0.76 nm RMSD 0.70 nm RMSD
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Refinement of an alternate model for 1afi
RMSD 0.87 nm RMSD 0.70 nm RMSD 0.76 nm
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Refinement of 1sro (PNPase) ROSETTA model NMR structure 0.87 nm RMSD
Fan Hao
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Refinement of 1sro (PNPase) NMR RMSD 0.88 nm RMSD 0.70 nm RMSD 0.67 nm
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