2. Modularity as an Organizing Principle in Protein Structure

3. Unequal recombination drives the repetition of structural elements TIM barrel muramidase x 300 Titin

4. Core of an average domain ~150 AA 20 different amino acids –> 20 150 = 10 200 different sequences Of these ~10 38 are expected to have different fold (i.e. less than 20% sequence identity) Estimated number of naturally occurring folds ~1000 Fraction of theoretically possible “folds” used in nature ~ 1/10 34 = 0.00000000000000000000000000000001%

5. Super secondary Structure elements

6. Structures with alpha-hairpin motifs

7. beta-hairpin Motifs

8. beta-alpha-beta Motif

13. Proteins with more than 30% AA identity almost always adopt the same fold.

14. folded unfolded Stability -  G folding Sequence Proteins as “Islands of Stability” in Sequence Space

15. Bridges in between islands Cordes et al. Nat. Struct. Biol 2000 Dec;7(12):1129-32.

16. Glykos, N.M., Cesareni, G. & Kokkinidis, M. (1999), Structure 7, 597-603

17. B1 domain of protein G Janus < 50% of AA changed Paracelsus Challenge