protein: linear chain of amino acids called residues (4 in this toy protein) ser trp leu o n n n n o...
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Protein: Linear chain of amino acidscalled residues (4 in this toy protein)
Ser
Trp
Leu
O
NN N
N
O O
CCCC
O
OCα
CαCα Cα
Lys
HH
H H
H
The backbone (red) is the same for all residues. The side-chains (green) vary.
The 20 amino acids found in nature
1-letter 3-letter Amino acid
A Ala Alanine
C Cys Cysteine
D Asp Aspartic Acid
E Glu Glutamic Acid
F Phe Phenylalanine
G Gly Glycine
H His Histidine
I Ile Isoleucine
K Lys Lysine
L Leu Leucine
1-letter 3-letter Amino Acid
M Met Methionin
N Asn Asparagine
P Pro Proline
Q Gln Glutamine
R Arg Arginine
S Ser Serine
T Thr Threonin
V Val Valine
W Trp Tryptophan
Y Tyr Tyrosine
Patrice Koehl
The Peptide Bond
CCN
Rn
OH
C
CN
ROH
n+1H
H
Peptide bond
The peptide bond is planar
Patrice Koehl
Degrees of Freedom in Proteins
1
2
34
+
Bond length
Bond angle
1 2
Dihedral angle
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Torsion angles avoid eclipsing
Torsion angles characterize residue conformation
Backbone: 3 angles per residue : ψ and
Sidechain: 1 to 7 angles, ; each has 3 favored values: 60o, -60o, 180o.
Patrice Koehl
φψ
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.
RAMACHANDRAN PLOTS
All residues, but glycine Glycine
Acta Cryst. (2002). D58, 768-776
Small Amino acids: Glycine
CA C
H
Highly flexible
Patrice Koehl
Hydrophobic Amino acids (1)
CA
CB
C
CH3
Ala
C
CH
CH3 CH3
CA
CB
CG1CG2
Val
Patrice Koehl
C
CH
CH3 CH3
CH2
CA
CB
CG
CD1
CD2
Hydrophobic Amino acids (2)
C
CH
CH2 CH3
CH3
CA
CB
CG1 CG2
CD
Leu Ile
Patrice Koehl
N C
CH2
CH2
CH2
CA
CB
CG
CD
N
Hydrophobic Amino acids (3)
C
CH2
C
CH CH
CH CH
CH
CA
CB
CG
CD1
CE1
CZ
CE2
CD2
Pro Phe Patrice Koehl
C
CH2
CH3
CH2
S
CA
CB
CG
SD
CE
Hydrophobic Amino acids (4)
C
CH2
C
CH
NC
C
HC
HCC
C HH
H
CA
CBCG
CD2CD1
NE1CE2
CE3
CZ2
CZ3
CH
Met Trp
Patrice Koehl
Polar Amino acids (1)
C
OH
CH2
CA
CB
OG
C
OH
CH
CA
CBOG1
CG2CH3
Ser Thr
Patrice Koehl
C
CH2
C
CH CH
CH CH
C
CA
CB
CGCD1
CE1
CZCE2CD2
OH
OH
Polar Amino acids (2)
Patrice Koehl
C
CH2
C
CA
CB CGND2
NH2O
OD1
Polar Amino acids (3)
C
CH2
CH2
C
CA
CB CG
CDNE2
NH2OOE1
Asn GlnPatrice Koehl
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
Polar Amino acids: Histidine
C
CH2
C
CH N
N C
H
H
pKa sidechain: 6.04CA
CBCG
ND1
CD2NE2
CE1
Patrice Koehl
C
CH2
CCH N
N C
H
H
C
CH2
CCH N
N CH
C
CH2
CCH N
N C
H
H
C
CH2
CCH N
N C
H
H
H
H
+
+
H
Different ionic states of the Histidine sidechain
Patrice Koehl
C
CH2
C
CA
CB
CGOD2
Charged Amino acids (1)
OOOD1
-
pKa sidechain: 3.9
C
CH2
CH2
C
CA
CB
CGCD
OE2OO
OE1 -
pKa sidechain: 4.25
Asp GluPatrice Koehl
C
CH2
CH2
CH2
pKa sidechain: 9.2
CH2
NH3+
CA
CB
CG
CDCE
NZ
Charged Amino acids (2)
C
CH2
CH2
CH2
NE
CZ
CA
CB
CG
CDNE
CZNH1
NH2
NH2 NH2+
pKa sidechain: 12.5
Lys Arg Patrice Koehl
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
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-Cα-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