Protein: Linear chain of amino acids
called residues (4 in this toy protein)
Leu
Ser
O
H
H
Cα
N
H
O
H
C
N
N Cα C
Cα
Cα
N
C
C
O
H
O
O
Trp
Lys
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
1-letter
3-letter
Amino Acid
A
Ala
Alanine
M
Met
Methionin
C
Cys
Cysteine
N
Asn
Asparagine
D
Asp
Aspartic Acid
P
Pro
Proline
E
Glu
Glutamic Acid
Q
Gln
Glutamine
F
Phe
Phenylalanine
R
Arg
Arginine
G
Gly
Glycine
S
Ser
Serine
H
His
Histidine
T
Thr
Threonin
I
Ile
Isoleucine
V
Val
Valine
K
Lys
Lysine
W
Trp
Tryptophan
L
Leu
Leucine
Y
Tyr
Tyrosine
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The Peptide Bond
Peptide bond
H
N
H
H
H
Ca
N
O
Rn
C
C
Ca
O
R n+1
The peptide bond is planar
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Degrees of Freedom in Proteins
Bond length
1
Dihedral angle
2
3
1
4
2
Bond angle
+
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Torsion angles avoid eclipsing
Torsion angles characterize residue
conformation
φ
ψ
Backbone: 3 angles per residue : f, ψ and w
Sidechain: 1 to 7 angles, c; each c has 3 favored values: 60o, -60o, 180o.
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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
y
y
f
All residues, but glycine
f
Glycine
Acta Cryst. (2002). D58, 768-776
Small Amino acids: Glycine
H
CA
C
Highly flexible
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Hydrophobic Amino acids (1)
CG2
CG1
CH3
CH3
CH3
CH
CB
CB
CA
C
C
CA
Ala
Val
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Hydrophobic Amino acids (2)
CD2
CD
CD1
CH3
CH3
CH3
CH
CG
CG1
CG2
CA
CH3
CH
CH2
CB
CH2
CB
C
C
CA
Leu
Ile
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Hydrophobic Amino acids (3)
CG
H
C
CE1
CB
CZ
CD1
CD
CE2
N
CA
CH2
CH2
CH2
N
Pro
CG
CH
CH
CH
CH
C
CD2
CB
CH2
CA
C
C
Phe
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Hydrophobic Amino acids (4)
CZ2
CE
CH3
NE1 CE2
S
SD
CG
CB
CH
H
C
CZ3
CE3
CH2
CG
C
C
HC
C
CD2
CD1
CH2
HC
H
N
CB
C
H
CH
C
CH2
C
CA
CA
Met
Trp
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Polar Amino acids (1)
CG2
OG1
CB
OH
OH
CB
CH3
CH
OG
CH2
C
C
CA
Ser
CA
Thr
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Polar Amino acids (2)
OH
OH
CE2
CD2
CZ
C
CH
CH
CH
CH
CE1
CD1
CG
CB
C
CH2
CA
C
Tyr
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Polar Amino acids (3)
OE1
OD1
O
ND2
CB
NH2
O
CD
C
CG
CB
Asn
C
C
CH2
CG
CH2
CA
NE2
NH2
CH2
C
CA
Gln
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Polar Amino acids: Cysteine
SG
CB
S
pKa sidechain: 8.3
CH2
C
CA
SG1
CB2
Can form disulphide bridges
in proteins
CB1
CA1
SG2
CA2
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Polar Amino acids: Histidine
NE2
CD2
CE1
N
CH
CH
CB
ND1
CG
N
H
C
CH2
C
CA
pKa sidechain: 6.04
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Different ionic states of the Histidine sidechain
H
+
N
CH
CH
N
H
C
H
N
CH2
CH
N
CH
C
CH
N
CH
C
CH2
C
N
H
C
H
N
CH2
CH
+
CH
N
C
H
C
CH2
C
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Charged Amino acids (1)
OD1
O-
O
CG
OD2
C
CB
OE1
OE2
CG
CD
CB
CH2
O
O
-
C
CH2
CH2
C
CA
CA
pKa sidechain: 3.9
Asp
C
pKa sidechain: 4.25
Glu
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Charged Amino acids (2)
NH2+
NH2
NZ
NH3+
NH1
NH2
CE
CD
CH2
CH2
CG
CZ
CZ
NE
CD
NE
CG
CH2
CH2
CH2
CB
CH2
CA
pKa sidechain: 9.2
Lys
C
CB
CH2
CA
C
pKa sidechain: 12.5
Arg
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Molecular Visualization Software
• PyMOL: the standard for publications
Brief youtube tutorial at:
http://www.youtube.com/watch?v=vDlyfk2zC-k
• Jmol
• MDL Chime
• RasMol
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 f , y , and w
• 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