1. Protein secondary structure prediction methods TDVEAAVNSLVNLYLQASYLS “From sequence to structure”

2. What are they? –Sequence-based tools for protein structure prediction. What do they do? 1.they Search for similar protein sequences in a database. 2.Based on the similarity to these sequences they predict aspects of protein structure and function

3. What kind of prediction can we perform? –S–Secondary Structure: Helix, Strands, Loops (PHDsec,PSIPRED). –P–Predicts transmembrane helices (PHDhtm,MEMSAT,TMHMM). –F–Fold structure (genTHREADER). –S–Solvent accessibility: important for the prediction of ligand binding sites (PHDacc). –O–Other features: Coiled Coils, Globular regions, Disulfide Bonds and more…

4. Secondary Structure prediction: Query SwissProt BLASTp Query Subject psiBLAST, MaxHom MSA Machine Learning Approach HHHLLLHHHEEE Known structures

5. PROF sec and PSIpred Two secondary structure prediction tools: PROFsec –Based on sequence family alignments (MAXHOM) PSIpred –Based on PSI-BLAST profiles

6. (PROFsec) http://www.predictprotein.org/

7. Input

8. List of results attached to your account Visual representation of a result

9. Output

11. PSIpred Input sequence Type of Analysis (PSIPRED,MEMSAT, genTHREAD) http://bioinf.cs.ucl.ac.uk/software_downloads/

12. http://bioinf.cs.ucl.ac.uk/web_servers/

13. PSIPRED secondary structure prediction

14. PROFsecPSIpred ? ?

15. TMHMM – transmembrane domain prediction http://www.cbs.dtu.dk/services/TMHMM/

17. Predict StartEnd

19. Sequence and Secondary Structure information

20. Sequence Details TurnHelix

21. Excersize The sequence below belongs to the Prion that causes the “mad cow” disease. This protein becomes toxic when it gets into the brain and misfolds causing native cellular prions to deform and aggregate. In structural terms, the prion toxicity in leaded by a folding change into an instable structure. >PRION_1ag2 GLGGYMLGSAMSRPMIHFGNDWEDRYYRENMYRYPNQVYYRPVDQYSNQNNFVHDCVNITIKQ HTVTTTTKGENFTETDVKMMERVVEQMCVTQYQKESQAYY 1.Use Predict Protein (PROFsec) to predict its secondary structures. 2.What is the secondary structure in the real solved structure based on the PDB? 3.Given the prediction results and the secondary structure of the real solved structure can you suggest the region which could be responsible for the structural instability?

22. 1. Predict Protein (PROFsec)

23. 2. PDB (DSSP)

24. 3. Answer : alpha helix PDB (DSSP) turn into B-sheet Predict Protein (ROFsec), prediction in this area are not consistent.