Protein structure prediction of CASP5 comparative modeling and fold recognition targets using consensus alignment approach and 3D assessment

AbstractComputational methods that produce accurate protein structure models from limited experimental data, e.g. from nuclear magnetic resonance (NMR) spectroscopy, hold great potential for biomedical research. The NMR-assisted modeling challenge in CASP13 provided a blind test to explore the capabilities and limitations of current modeling techniques in leveraging NMR data which had high sparsity, ambiguity and error rate for protein structure prediction. We describe our approach to predict the structure of these proteins leveraging the Rosetta software suite. Protein structure models were predictedde novousing a two-stage protocol. First, low-resolution models were generated with the Rosettade novomethod guided by non-ambiguous nuclear Overhauser effect (NOE) contacts and residual dipolar coupling (RDC) restraints. Second, iterative model hybridization and fragment insertion with the Rosetta comparative modeling method was used to refine and regularize models guided by all ambiguous and non-ambiguous NOE contacts and RDCs. Nine out of 16 of the Rosettade novomodels had the correct fold (GDT-TS score >45) and in three cases high-resolution models were achieved (RMSD <3.5 Å). We also show that a meta-approach applying iterative Rosetta+NMR refinement on server-predicted models which employed non-NMR-contacts and structural templates leads to substantial improvement in model quality. Integrating these data-assisted refinement strategies with innovative non-data-assisted approaches which became possible in CASP13 such as high precision contact prediction will in the near future enable structure determination for large proteins that are outside of the realm of conventional NMR.

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Combining local-structure, fold-recognition, and new fold methods for protein structure prediction

Proteins Structure Function and Bioinformatics ◽

10.1002/prot.10540 ◽

2003 ◽

Vol 53 (S6) ◽

pp. 491-496 ◽

Cited By ~ 191

Author(s):

Kevin Karplus ◽

Rachel Karchin ◽

Jenny Draper ◽

Jonathan Casper ◽

Yael Mandel-Gutfreund ◽

...

Keyword(s):

Protein Structure ◽

Protein Structure Prediction ◽

Local Structure ◽

Structure Prediction ◽

Fold Recognition

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Computational Methods for Protein Structure Prediction and Fold Recognition

Practical Bioinformatics - Nucleic Acids and Molecular Biology ◽

10.1007/978-3-540-74268-5_1 ◽

2008 ◽

pp. 1-21 ◽

Cited By ~ 5

Author(s):

Iwona A. Cymerman ◽

Marcin Feder ◽

Marcin PawŁowski ◽

Michal A. Kurowski ◽

Janusz M. Bujnicki

Keyword(s):

Protein Structure ◽

Protein Structure Prediction ◽

Computational Methods ◽

Structure Prediction ◽

Fold Recognition

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Generalized comparative modeling (GENECOMP): A combination of sequence comparison, threading, and lattice modeling for protein structure prediction and refinement

Proteins Structure Function and Bioinformatics ◽

10.1002/prot.1080 ◽

2001 ◽

Vol 44 (2) ◽

pp. 133-149 ◽

Cited By ~ 70

Author(s):

A. Kolinski ◽

M.R. Betancourt ◽

D. Kihara ◽

P. Rotkiewicz ◽

J. Skolnick

Keyword(s):

Protein Structure ◽

Protein Structure Prediction ◽

Sequence Comparison ◽

Structure Prediction ◽

Comparative Modeling

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Sequence Specific Dihedral Angle Distribution: Application in Protein Structure Prediction and Evaluation

Plant Tissue Culture and Biotechnology ◽

10.3329/ptcb.v19i2.5439 ◽

1970 ◽

Vol 19 (2) ◽

pp. 217-226

Author(s):

S. M. Minhaz Ud-Dean ◽

Mahdi Muhammad Moosa

Keyword(s):

Protein Structure ◽

Dihedral Angle ◽

Protein Structure Prediction ◽

Structure Prediction ◽

Protein Structures ◽

Angle Distribution ◽

Ramachandran Plot ◽

Specific Data ◽

Specific Distribution ◽

Structure Evaluation

Protein structure prediction and evaluation is one of the major fields of computational biology. Estimation of dihedral angle can provide information about the acceptability of both theoretically predicted and experimentally determined structures. Here we report on the sequence specific dihedral angle distribution of high resolution protein structures available in PDB and have developed Sasichandran, a tool for sequence specific dihedral angle prediction and structure evaluation. This tool will allow evaluation of a protein structure in pdb format from the sequence specific distribution of Ramachandran angles. Additionally, it will allow retrieval of the most probable Ramachandran angles for a given sequence along with the sequence specific data. Key words: Torsion angle, φ-ψ distribution, sequence specific ramachandran plot, Ramasekharan, protein structure appraisal D.O.I. 10.3329/ptcb.v19i2.5439 Plant Tissue Cult. & Biotech. 19(2): 217-226, 2009 (December)

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