1. PROTEIN PHYSICS LECTURE 15

2. Protein Structures & Physical Background of Their Natural Selection  Structures  Selection

3. GlobulardomainsCATHSCOP

4. Efimov’s “trees”

5. We do not see difference of folds of globular proteins of pro- and eukariotes. However, we see that eukariotic proteins are larger, contain more domains, and are more modified. Adaptive evolution of protein structures: Microscopic adaptive changes; Domain duplication an divergence.

6. J.Richardson, 1977 TYPICAL FOLDING PATTERNS

8. EMPIRICAL RULES for FREQUENT FOLDS   and   structures, right-handed separate  and  layers superhelices no large (360-degree) turns no loop crossing Lost H-bonds: defect!

9. Unusual fold (no , almost no  structure) Special sequence (very many S-S bonds) RARE FOLDS, e.g.:

10.  -sheet: INSIDE

11. Unusual fold (GFP)

12. What is better:   inside or    inside?   N>150

13. _____ ____

14. Miller,Janin,Chothia1984 Example:Smallproteindetails

15. THEORYClosedsystem:energy E = const CONSIDER: 1 state of “small part” with  & all states of thermostat with E- . M(E-  ) = 1 M th (E-  ) S t (E-  ) = k ln[M t (E-  )]  S t (E) - (dS t /dE)| E M t (E-  ) = exp[S t (E)/k] exp[- (dS t /dE)| E /k] WHAT IS “TEMPERATURE”? S ~ ln[M] Thus: (dS t /dE)| E = 1/ T; d[ln(M t )]/dE = 1/kT

16. Protein structure is stable, if its free energy is below some threshold For example: below that of completely unfolded chain; or: below that of any other globular structure

20. “Multitude principle” for physical selection of folds of globular proteins (“designability”): the more sequences fit the given architecture without disturbing its stability, the higher the occurrence of this architecture in natural proteins.

22. Hydrophobic patterns necessary for secondary structures Secondary structure patterns (  3 turns, as in globular proteins) are randomly formed in random sequences