The presentation was given at the CIBCB, 2005, in San Diego about our approach to predict recombination sites in protein sequence. Recombination is the method of choice for designing new proteins with desired new or enhanced properties. The publication is : Bauer, D.C., Bodén, M., Thier, R. and Gillam, E. M. “STAR: Predicting recombination sites from amino acid sequence.” BMC Bioinformatics, 2006 Oct 8; 7:437. PMID: 17026775

1. Predicting structural disruption caused by crossover : a machine learning approach Denis C. Bauer Talk CIBCB 2005

6. Benefit of Recombination KEMHQPLTFGELENLPLLNTDKPVQALM Problem: how to identify recombination sites ? Introduction KIPDELGLIFKFEAPGRVTRVLSSQ … M H K L N E K A P TIKELPQPPTFGELKKLPLLNTDKPVQAL M L K P G K G MKIADELGEIFKFEAPGRVTRYLSSQ… A P E L Y A Better resistant to heat Higher performance Higher performance Better resistant to heat Mayfly Lives where its hot MKIPDELGLIFKFEAPGRVTRALSSQ… MKIPDELGLIFKFEAPGRVTRALSSQ… KEMHQPLTFGELENLPLLNTDKPVQAL KEMHQPLTFGELENLPLLNTDKPVQAL

9. Our approach

10. Alternative to SCHEMA 3D Structure Information Schema Alg Schema Score Predicting Sequence Benefit: All Proteins can be processed Our Approach

11. Predicting Schema-Profile Predicted Schema Score Sequence Support Vector Regression Predictive Model * * Bodén, M., Yuan, Z. and Bailey, T. L. Prediction of protein continuum secondary structure with probabilistic models. submitted Our Approach Model Bidirectional Recurrent Network Feed Forward Neural Network

12. Results Table 1 Results for all approaches. r = correlation coefficient (ideally 1), devA = Root Mean Square Error (RMSE) normalized by the standard deviation (ideally 0). Results 0.62 0.83 SVR nu 0.63 0.82 SVR eps 0.52 0.88 BRNN 0.57 0.86 FFNN devA r Method

13. Results Results

14. Results Results

15. Refinements Contact Numbers Predicting Model Predicted Schema Score predicted Input features Solvent Accessibility Score CC 0.88 0.88 0.6 Ensemble 0.88 Results ML model ML model ML model ML model

19. Thank you Ref: C. A. Voigt, C. Martinez, Z.-G. Wang, S. L. Mayo, and F. H. Arnold, Protein building blocks preserved by recombination, Nat Struct Biol, vol. 9, no. 7, pp. 553-558, Jul 2002. Meyer MM, Silberg JJ, Voigt CA, Endelman JB, Mayo SL, Wang ZG, Arnold FH. Library analysis of SCHEMA-guided protein recombination. Protein Sci. 2003 Aug;12(8):1686-93. Bodén, M., Yuan, Z. and Bailey, T. L. Prediction of protein continuum secondary structure with probabilistic models. submitted.

20. PDB 1zg4