1. covalent interactions non-covalent interactions + = structural stability of (bio)polymers in the operative molecular environment 1 Energy, entropy and reaction coordinate (Q) of molecular folding process

2. covalent interactions non-covalent interactions disulfide bridges in proteins: 2

3. 3

4. non-covalent interactions in proteins: 4

5. 5 energy contribution not dependent on molecular environment

6. 6

7. 7

8. 8

9. 9

10. 10 energy contribution not dependent on molecular environment

11. 11 influenced by solvent electrostatic interactions electrostatic interactions dipolar interactions dipolar interactions hydrogen bonding hydrogen bonding

12. 2a. enthalpy and entropy in protein folding 12 hydrogen bond

13. 13 hydrogen bond 2a. enthalpy and entropy in protein folding

14. 14 hydrogen bond 2a. enthalpy and entropy in protein folding

15. electrostatic interactions 15

16. 16

17. 17 solvent dependent hydrophobic interactions hydrophobic interactions direct interations with solvents direct interations with solvents

18. The vdW surface of a molecule (shown in red) is defined as the surface of the union of balls representing all atoms, with radii set to the vdW radii. The accessible surface of the same molecule (shown in green) is the surface generated by the center of a sphere rolling on the vdW surface. The radius of this sphere is usually set to 1.4 Angstroms, the radius of a water molecule. The molecular surface (shown in magenta) is the lower envelope generated by the rolling sphere. It differs from the vdW surface in that some areas are inaccessible to the rolling sphere. The accessible surface of a protein is defined as the van der Waals envelope of the molecule expanded by the radius of the solvent sphere about each atom center (Lee, B and Richards, FM. The interpretation of protein structure: estimation of static accessibility. J. Mol. Biol., 55, 379-400 (1971) 18

19. 19

20. 20

21. TOTAL CONFORMATIONAL ENERGY E=E a +E r +E es +E l +E t +E f +E H +E Hf E a attractive E r repulsive E es electrostatic potential E l bond lenght changes E t bond angle changes E f torsional potential E H hydrogen bond Eh f hydrophobic interactions FORCE FIELD 21

22. 2a. enthalpy and entropy in protein folding 22 from http://www.lanl.gov/bmsi/Individual%20Research/Werner/WernerFolding.html from http://employees.csbsju.edu/hjakubowski/classes/ch331/protstructure/olhydrophobprot.html thermodynamics of protein folding

23. 2a. enthalpy and entropy in protein folding 23