791_ak_lecture5

791_ak_lecture5 - 7.91 Amy Keating Methods for Protein...

Info iconThis preview shows pages 1–9. Sign up to view the full content.

View Full Document Right Arrow Icon
Methods for Protein Structure Prediction Homology Modeling & Fold Recognition Next time: Ab Initio Prediction 7.91 Amy Keating
Background image of page 1

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon
Review - Homology Modeling Identify a protein with similar sequence for which a structure has been solved (the template ) Align the target sequence with the template Use the alignment to build an approximate structure for the target Fill in any missing pieces Fine-tune the structure Evaluate success An excellent review: Marti-Renom et al. Annu. Rev. Biophys. Biomol. Struct. 29 (2000): 291-325.
Background image of page 2
these numbers are from an entirely automated process - can do better with manual intervention Marti-Renom et al. Annu. Rev. Biophys. Biomol. Struct. 29 (2000): 291-325. Courtesy of Annual Reviews Nonprofit Publisher of the Annual Review of TM Series. Used with permission.
Background image of page 3

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon
Homology Modeling on a Genomic Scale Requires automation – Can’t choose templates or fine-tune the alignment by hand! MODBASE and 3D-CRUNCH http://alto.compbio.ucsf.edu/modbase-cgi/index.cgi http://www.expasy.ch/swissmod/SM_3DCrunch.html Automatic assessment is critical - how reliable is the model?
Background image of page 4
One approach to assessment Want to compute the probability that a prediction is good, based on properties of the model For a given score of the model (e.g. Q-score - more on this later), use a training set of known examples, together with Bayes’ rule P(A|B) = P(A ^ B)/P(B) = P(A)P(B|A)/{P(A)P(B|A) + P(!A)P(B|!A)} Assume probability of a good vs. a bad model is the same, i.e. P(A) = P(!A) where A = good model; !A = bad model; B = Q-score P(good|Q-score) = P(Q-score|good)/{P(Q-score|good) + P(Q-score|bad)} Prob. Q-score good models bad models Sanchez, R, and A Sali. "Large-scale Protein Structure Modeling of The Saccharomyces Cerevisiae Genome." Proc Natl Acad Sci U S A. 95, no. 23 (10 November 1998): 13597-602.
Background image of page 5

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon
MODBASE http://alto.compbio.ucsf.edu/modbase-cgi/index.cgi • 733,239 sequences & 7,120 non-redundant structures Fold Assignments (by PSI-BLAST) • Reliable fold assignments: 827,007 for 413,311 sequences • Average folds per sequence: 2.0 • Average length of queries: 511 amino acids •A v e r a g e l e n g t h o f folds: 229 amino acids Comparative Models (by MODELLER) • Reliable models 547,473 • Sequences with reliable models: 327,393 (59%) • Structures used as templates: 6.366 (89%) For a reliable fold assignment, PSI-BLAST E value < 0.0001 OR a reliable model. For a reliable model, 30% of C α atoms superpose within 3.5Å of their correct positions
Background image of page 6
Example You’ve just cloned a new gene from Pombe - look it up in ModBase putative galactosyltransferase associated protein kinase (GenBank accession # 3006192) Pieper, Ursula, Narayanan Eswar, Ashley C. Stuart, Valentin A. Ilyin, and Andrej Sali. "MODBASE, A Database of Annotated Comparative Protein Structure Models." Nucl. Acids Res. 30 (2002): 255-259. http://alto.compbio.ucsf.edu/modbase-cgi/index.cgi
Background image of page 7

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon
Model of new POMBE gene TEMPLATE = 1HCL TARGET PDB ID: 1HCL Schulze-Gahmen, U., J. Brandsen, H. D. Jones, D. O. Morgan, L. Meijer, J. Vesely, and S. H. Kim. "Multiple Modes of Ligand Recognition: Crystal Structures of Cyclin-dependent Protein Kinase 2 in Complex with ATP and Two Inhibitors, Olomoucine and Isopentenyladenine."
Background image of page 8
Image of page 9
This is the end of the preview. Sign up to access the rest of the document.

This note was uploaded on 11/11/2011 for the course BIO 20.410j taught by Professor Rogerd.kamm during the Spring '03 term at MIT.

Page1 / 41

791_ak_lecture5 - 7.91 Amy Keating Methods for Protein...

This preview shows document pages 1 - 9. Sign up to view the full document.

View Full Document Right Arrow Icon
Ask a homework question - tutors are online