1. PDB-Protein Data Bank SCOP –Protein structure classification CATH –Protein structure classification genTHREADER–3D structure prediction Swiss-Model–3D structure prediction ModBase-A database of 3D struc. Predict. Protein Structure Prediction II

4. PDB file Accession number Java based visualization tools Structural Classification

5. PDB provides the atomic coordinates of the structure : Which can be viewed by different visualization tools

7. SCOP: Structural Classification of Proteins http://scop.mrc-lmb.cam.ac.uk/scop/ Based on known protein structures Manually created by visual inspection Hierarchical database structure: –Class, Fold, Superfamily, Family, Protein and Species

9. Parents of node Children of node Node

10. Parents of node Children of node Node

14. CATH: Protein Structure Classification by Class, Architecture, Topology and Homology http://www.cathdb.info/ Class: The secondary structure composition: mainly-alpha, mainly-beta and alpha-beta. Architecture: The overall shape of the domain structure. Orientations of the secondary structures : e.g. barrel or 3- layer sandwich. Topology: Structures are grouped into fold groups at this level depending on both the overall shape and connectivity of the secondary structures. Homologous Superfamily: Evolutionary conserved structures

16. CATH: Protein Structure Classification by Class, Architecture, Topology and Homology

17. genTHREADER Input sequence Type of Analysis (PSIPRED,MEMSAT, genTHREAD) http://bioinf.cs.ucl.ac.uk/psipred/psiform.html

18. GenTHREADER Output

19. GenTHREADER Output The output sequences show some extent of sequence homology But high level of secondary structure conservation

20. SWISS-MODEL An automated protein modeling server. http://swissmodel.expasy.org/

21. SWISS-MODEL The SWISS-MODEL algorithm can be divided into three steps: 1.Search for suitable templates: the server finds all similarities of a query sequence to sequences of known structure. It uses the BLASTP2 program with the ExNRL-3D database (a derivative of PDB database, specified for SWISS-MODEL). You get these partial results as a SwissModel TraceLog file. 2.Check sequence identity with target: All templates with sequence identities above 25% are selected 3.Create the model using the ProModII program. You get this as a SwissModel-Model file.

22. SWISS-MODEL Get PDB file by E-mail Load to J-Mol

23. Single Structure Homology Modeling

24. Swiss-Model file Structures used for the homology model query

25. Comparative Modeling Accuracy of the comparative model is related to the sequence identity on which it is based >50% sequence identity = high accuracy 30%-50% sequence identity= 90% modeled <30% sequence identity =low accuracy (many errors)

26. ModBase A Homology Model Database http://modbase.compbio.ucsf.edu/modbase-cgi/index.cgi

29. Ligand Binding Site

30. 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 Use PSIpred, geneTHREADER and PROFsec in order to predict its secondary and tertiary structures. Based on the secondary and tertiary structure predictions 1.Can you suggest the region which could be responsible for the structural instability? 2.What is the secondary structure in the real solved structure? 3.What is the expected structural change in this region?

31. PSIPRED

32. geneTHREADER

33. PROFsec

34. Answer : alpha helix geneTHREADER turn into B-sheet PSIPRED anf PROFsec, prediction in this area are not consistent in the different tools.