1. Protein: Linear chain of amino acids called residues (4 in this toy protein) Ser Trp Leu O N N N N O O C C C C O O CαCα CαCα CαCα CαCα Lys H H H H H The backbone (red) is the same for all residues. The side-chains (green) vary.

2. The 20 amino acids found in nature 1-letter3-letterAmino acid AAlaAlanine CCysCysteine DAspAspartic Acid EGluGlutamic Acid FPhePhenylalanine GGlyGlycine HHisHistidine IIleIsoleucine KLysLysine LLeuLeucine 1-letter3-letterAmino Acid MMetMethionin NAsnAsparagine PProProline QGlnGlutamine RArgArginine SSerSerine TThrThreonin VValValine WTrpTryptophan YTyrTyrosine

3. Patrice Koehl

4. The Peptide Bond CC C N RnRn O H CC C N R O H n+1 H H Peptide bond The peptide bond is planar Patrice Koehl

5. Degrees of Freedom in Proteins 1 2 3 4 + Bond length Bond angle 12 Dihedral angle Patrice Koehl

6. Torsion angles avoid eclipsing

7. Torsion angles characterize residue conformation Backbone: 3 angles per residue :  ψ and  Sidechain: 1 to 7 angles,  ; each  has 3 favored values: 60 o, -60 o, 180 o. Patrice Koehl φ ψ

8. Proteins fall to lowest free energy conformation Protein Folding in the Landscape Perspective: Chevron Plots and Non-Arrhenius Kinetics Hue Sun Chan and Ken A. Dill, Proteins: Structure, Function, and Genetics, 30:1 Free energy (vertical axis) as a function of conformation. The two horizontal axes represent torsional degrees of freedom.

9. RAMACHANDRAN PLOTS All residues, but glycineGlycine   Acta Cryst. (2002). D58, 768-776

10. Small Amino acids: Glycine CAC H Highly flexible Patrice Koehl

11. Hydrophobic Amino acids (1) CA CB C CH3 Ala C CH CH3 CA CB CG1CG2 Val Patrice Koehl

12. C CH CH3 CH2 CA CB CG CD1 CD2 Hydrophobic Amino acids (2) C CH CH2CH3 CA CB CG1 CG2 CD Leu Ile Patrice Koehl

13. NC CH2 CA CB CG CD N Hydrophobic Amino acids (3) C CH2 C CH C H CA CB CG CD1 CE1 CZ CE2 CD2 Pro Phe Patrice Koehl

14. C CH2 CH3 CH2 S CA CB CG SD CE Hydrophobic Amino acids (4) C CH2 C CH N C C HC C C H H H CA CB CG CD2 CD1 NE1 CE2 CE3 CZ2 CZ3 CH Met Trp Patrice Koehl

15. Polar Amino acids (1) C OH CH2 CA CB OG C OH CH CA CB OG1 CG2 CH3 Ser Thr Patrice Koehl

16. C CH2 C CH C CA CB CG CD1 CE1 CZCE2 CD2 OH Polar Amino acids (2) Patrice Koehl

17. C CH2 C CA CBCG ND2 NH2O OD1 Polar Amino acids (3) C CH2 C CA CB CG CD NE2 NH2O OE1 Asn Gln Patrice Koehl

18. Polar Amino acids: Cysteine C S CH2 CA CB SG CB1 SG1 SG2 CB2 CA1 CA2 Can form disulphide bridges in proteins pKa sidechain: 8.3 Patrice Koehl

19. Polar Amino acids: Histidine C CH2 C CHN NC H H pKa sidechain: 6.04 CA CB CG ND1 CD2 NE2 CE1 Patrice Koehl

20. C CH2 C CHN NC H H C CH2 C CHN NCH C CH2 C CHN NC H H C CH2 C CHN NC H H H H + + H Different ionic states of the Histidine sidechain Patrice Koehl

21. C CH2 C CA CB CG OD2 Charged Amino acids (1) OO OD1 - pKa sidechain: 3.9 C CH2 C CA CB CG CD OE2 OO OE1 - pKa sidechain: 4.25 Asp Glu Patrice Koehl

22. C CH2 pKa sidechain: 9.2 CH2 NH3 + CA CB CG CD CE NZ Charged Amino acids (2) C CH2 NE CZ CA CB CG CD NE CZ NH1 NH2 NH2 + pKa sidechain: 12.5 Lys Arg Patrice Koehl

23. Molecular Visualization Software Pymol: the standard for publications youtube tutorial at: http://www.youtube.com/watch?v=vDlyfk2zC-k A more complete tutorial can be found at: http://www.ebi.ac.uk/~gareth/pymol/ Jmol DS Visualizer displays rotamers off of a common mainchain

24. Summary Proteins in nature are a string of residues, each of which is one of the 20 amino acids. Amino acids all have a backbone made of atoms N-C α -CO in a conformation characterized by the torsion angles,, and The remaining atoms form side-chains whose conformations are characterized by their torsion angles. Side-chains can be hydrophobic, polar or charged. Hydrophobic amino acids: GLY,ALA,VAL,ILE,LEU,PHE,PRO,MET,TRP Polar amino acids: CYS, SER, THR, HIS, ASN, GLN, TYR Charged amino acids: ASP, GLU, ARG, LYS  