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Predicting functional surface patches on protein structural models

Predicting functional surface patches on protein structural models. Iris Dror *, Shula Shazman *, Srayanta Mukherjee , Yang Zhang, Fabian Glaser and Yael Mandel- Gutfreund. Patch Finder Plus. PFPlus extract and display the largest positive electrostatic patch on a protein surface.

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Predicting functional surface patches on protein structural models

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  1. Predicting functional surface patches on protein structural models • Iris Dror*, Shula Shazman*, SrayantaMukherjee, Yang Zhang, Fabian Glaser and Yael Mandel-Gutfreund

  2. Patch Finder Plus • PFPlus extract and display the largest positive electrostatic patch on a protein surface. • It was shown that the largest positive electrostatic patch of a solved structure is highly overlap with the real nucleic acid binding interface. Shazman S, Patch Finder Plus (PFplus): a web server for extracting and displaying positive electrostatic patches on protein surfaces Nucleic Acids Res. (2007).

  3. Predicting binding interface • This was shown only for protein which already have a solved structure. Can we also predict the binding interface for a protein that doesn’t have a solved structure? Shazman S, Patch Finder Plus (PFplus): a web server for extracting and displaying positive electrostatic patches on protein surfaces Nucleic Acids Res. (2007).

  4. I-TASSER protein structure prediction • Predicting protein structures for 74 NA binding proteins using I-TASSER (those 74 proteins have a solved structure). • I-TASSER was ranked as the best performing structure prediction modeling server.

  5. I-TASSER protein structure prediction Yang Zhang. I-TASSER server for protein 3D structure prediction. BMC Bioinformatics, (2008).

  6. What we have • Model patch. • Solved patch. • NA interface. Cyan – largest patch Blue- largest patch Orange – interface • See if the largest positive patch of the predicted structure can be used to predict the NA interface.

  7. Calculations • Solved patch (Blue). • Model patch (Red). TN How much from our model patch is in the solved patch. How much from the solved patch we were able to predict. FN FP TP Combine both measurements

  8. Model patch vsSolved patch • Median MCC ~0.3. • No significant difference between the 5 models.

  9. Multiple models information • Can we use multiple models information to improve the prediction of the largest positive patch? Less strict More strict

  10. Multiple Models vs Solved patch • Sensitivity improves when we are less strict. • PPV improves when we are more strict. • The best balanced combined patch constructed from AAs that were found in at least 3.

  11. Multiple Models / Solved vs NA Interface • Can we predict NA interface? • MCC of combined 3 models (0.32) similar to the solved structure (0.39). • The PPV of the combined 5 is even better then the solved structure.

  12. Levels of reliabilities C A B • Largest electrostatic patch calculated on the crystal structure • NA-binding interface extracted from the crystal structure • Colored according to the model patch levels: Blue for level 5 cyan for level 4 and light green for level 3. All other AA are colored white.

  13. Conclusion • Predicted structure with combined patch can be used to find the NA interface of a NA binding protein. • This approach can be used for many applications.

  14. Thank you for listening • Shula Shazman • Srayanta Mukherjee • Yang Zhang • Fabian Glaser • and Yael Mandel-Gutfreund

  15. Supplement

  16. Supplement

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