1. Introduction & overview
PROTEIN PHYSICS
LECTURE 1
Introduction & overview

2. Globular
proteins
Membrane
proteins
Fibrous proteins
H-bonds (NH:::OC) & hydrophobic forces

3. Protein chain
(gene-encoded sequence)

4. PROTEIN HAS DEFINITE 3D STRUCTURE Homologous (closely related)
proteins
One protein - various
crystallization, NMR
Secondary structures (a-helices, b-strands)
are most conserved structural elements.
They form a basis of protein classification

7. Globular proteins
Sequence
&
Structure
Membrane
proteins
Fibrous proteins
H-bonds (NH:::OC) & hydrophobic forces

8. C A T H
Globular
domains

9. CAN FORM ITS UNIQUE 3D STRUCTURE
PROTEIN CHAIN
CAN FORM ITS UNIQUE 3D STRUCTURE
SPONTANEOUSLY
IN VITRO

10. BIND  TRANSFORM  RELEASE:
ENZYMES (chymotrypsin)
Note small active site

11. non-active cat. site active cat. site POST-TRANSLATIONAL MODIFICATIONS
Sometimes,
CHAIN CUT-INDUCED DEFORMATION MAKES ENZYME ACTIVE
non-active cat. site
active cat. site
Chymotripsin Chymotripsinogen

12. POST-TRANSLATIONAL MODIFICATIONS: (especially in eukaryotes): PROTEIN CHAIN CUTS (proteolysis), SPLICING (inteins) CYCLIZATION INTERNAL CHEM. TRANSFORMATION GLYCOSYLATION, etc. MODIFICATION OF ENDS (acetylation, etc.) MODIFICATION OF SIDE CHAINS (S-S bonding, phosphorilation, etc.) COFACTORS …

13. Different folds with the same active site:
Sometimes:
Different folds with the same active site:
the same biochemical function

14. COFACTORS: HEME, 2Fe, RNA, …
4-helix bundle
COFACTORS: HEME, 2Fe, RNA, …
Sometimes:
Similar folds with different active sites: different biochemical function

15. Standard positions of active sites in protein folds

16. Elementary interactions:
PROTEIN PHYSICS
LECTURE 2
Elementary interactions:
covalent

17. gene-encoded sequence
Protein chain:
regular backbone
&
gene-encoded sequence
of side chains

18. Covalent bond lengths:
Protein chain
Covalent bond lengths:
0.9 – 1.8 Å
Covalent bond angles:
109o – 120o
Atom radii:
1 – 2 Å

19. Side chains

20. Side chains: L-amino acids
Protein chain
Side chains: L-amino acids
___
______
______
Main-chain
peptide group:
flat & rigid

21. backbone- side_chain:
Gly
asymmetric
backbone- side_chain:
Ala _L
Thr
Two
asymmetric
side
chains:
Ile

23. Peptide group:
flat & rigid
sp2 + p sp2 + p
Covalent bonding

24. Main-chain:
f (N-Ca) ,
y (Ca-C’),
w (C’=N)
Side-chain:
c1, c2, ...

25. _____________________________________________
Counting
angles:
120o
180o 0o
_____________________________________________

26. sp2 - sp2 (w)
w = 180o w = 0o

27. Potentials: from IR spectra of vibrations
_____________________________________________
classical
Pro
sp2 - sp2 (w)
All,
but Pro
sp3 – sp3 (c)
C-CH2-CH2-C
CH3-CH3
sp2 – sp3 (f, y)