Download Side chains are negatively charged

Nucleotide and Pairing
Universal
Genetic
Code
Genetic Code Properties
• Purine (A,G) is heavier than Pyrimidine (C,T)
• Transition within a type (Purines or Pyrimidineㄴ) is more
likely than Translation between types
• All AAs have more than one codon, except for Met and Trp
• Codons for an AA are clustered
– Two codons for an AA – same in the first 2 positions and
differ only by transition at the 3rd position
– Four codons – differ only in the 3rd position
– Six codons – form one four-codon box and one twocodon box
Genetic Code
X
• Degeneracy is controlled by
GC content of codons
– G-C binding is stronger
– First two bases (doublets) are
GC – form four codon boxes
(red X)
– Doublets are AU – split boxes
(blue X)
– Doublets are mixed



X
X
X
X
X
X
X
Purine
2nd base is pyrimidine (C,T) – four codon boxes, split otherwise
Larger purine at the 2nd position reduces binding at the 3rd position
A doublet forms a four-codon box, its ‘conjugate’ forms a split box
 Conjugate – opposite size and opposite number of hydrogen
bonds; A-C and G-U are conjugates
Genetic Code

Five most hydrophobic – Phe, Leu, Ile, Met, Val
 U at the 2nd position
 Three most similar – Leu, Ile, Val


Single-base mutation at 1st position
Six most hydrophilic – His,Gln,Asn,Lys,Asp, Glu
 A at the 2nd position

(Tyr is hydrophobic and has A in 2nd position)
Evolution of Genetic Code
• From what the current Genetic Code became stable ?
• Robin Knight
– www.cs.uml.edu/~kim/580/99_knight.pdf
Amino Acids

General structure of amino
acids




an amino group
a carboxyl group
α-carbon bonded to a hydrogen and
a side-chain group, R
R determines the identity of
particular amino acid
•
•
•
•
•
R: large white and gray
C: black
Nitrogen: blue
Oxygen: red
Hydrogen: white
(Hydrophobic)
(uncharged polar)
(positively charged)
(negatively charged)
AA Groups

Classification of R groups


According to propensity to be in contact with
polar solvent like water
 Nonpolar (Hydrophobic) – many carbons in
R
 Polar
 Charged (hydrophilic)
 Acidic – negatively charged
 Basic – positively charged
 Uncharged polar
Polar/nonpolar
 Polar share electron bonds unequally
 O-H bond is polar: O is more electro-negative
and bonding electrons are closer to O
 C-H is nonpolar
Element
Electronegativty
Oxygen
3.5
Nitrogen
3.0
Sulfur
2.6
Carbon
2.5
Phosphorus 2.2
Hydrogen
2.1
Group 1: Nonpolar (hydrophobic)

Sometimes, Gly (G) is included because C-H bond is nonpolar
Group 2: Polar

Side chains are electronically neutral (uncharged)


Ser (S), Thr (T), Cys (C), Asn (N), Gln (Q), Try (Y)
Asn (N) and Gln (Q) are consider derivatives of group 3 Asp (D) and
Glu (E)
Group 3: Acidic

Side chains have carboxyl group


Asp (D) and Glu (E)
Side chains are negatively charged
Group 4: Basic
• Side chain is
positively charged
– His (H), Lys
(K), Arg (R)
Vol.
Physico-Chemical Properties
• Physico-chemical properties of AA determine
protein structures
– bioinformatics can be used via a pattern recognition
• Properties
– (1) Size in volume



Volume occupied by side groups is important
(also for molecular evolution), and difficult to
substitute a large AA for a small one
Van der Waals radius (volume until atoms are
pushed to repulsion) is used to measure the
volume of the sphere (in Å3)
W has 3.4 times the volume of G
Alanine
Ala
A
67
Arginine
Arg
R
148
Asparagine
Asn
N
96
Aspartic
Asp
D
91
Cysteine
Cys
C
86
Glutamine
Gln
Q
114
Glycine
Gly
G
48
Histidine
His
H
118
Isoleucine
Ile
I
124
Leucine
Leu
L
124
Lysine
Lys
K
135
Methionine
Met
M
124
Phenyl.
Phe
F
135
Proline
Prot
P
90
Serine
Ser
S
73
Threonine
Thr
T
93
Tryptophan
Trp
W
163
Tyrosine
Thr
Y
141
Valine
Val
V
105
Mean
109
(2) Partial Vol.
–
•
Measure expanded volume in solution when dissolved
(3) Bulkiness
–
•
•
•
The ratio of side chain volume to its length
Measure of average cross-sectional area of the side chain
Relevant to protein folding
(4) Polarity index
–
•
Electrostatic force acting on its surrounding at a distance of 10 Å
(5) pH of isoelectric point of AA (pI)
–
•
•
•
Acidic Asp and Glu have pI in 2-3: negatively charged at neutral pH
due to ionization of COOH group to COO- -- need to put them in an
acid solution to shift equilibrium and balance this charge (side chain
is charged +)
Basic (Arg, Lys and His) has pI >7 (charged -)
All others have uncharged side chains (pl. in 5-6)
–
(6) Hydrophobicity
•
•
•
•
•
•
–
(7) Surface area
•
•
–
When molecules are dissolved in water, hydrogen-bonded structure is
disrupted
Polar AA residues can form hydrogen bonds with water –hydrophilic
Non-polar that cannot form the bonds – hydrophobic
Polar disrupts the structure less than non-polar
Polar is usually at the exterior of a structure, non-polar, interior
Hydrophobicity (hydropathy) scale: estimate of difference in free
energy of AA when buried in hydrophobic environment of the interior
of a protein in water solution (+ for hydrophobic – costs free energy
to take residue out of protein and put it in water)
Surface area of AA exposed (accessible) to water in an unfolded
peptide chain and become buried when the chain folds
Relevant to protein folding
(8) Fraction of area
•
•
Fraction of the accessible surface area that is buried in the interor in
a set of known crystal structures
Hydrophobic residues have a larger fraction
Red: acidic
Orange: basic
Green: polar
Yellow: nonpolar
Vol.
Bulk
Pol.
pI
Hydro
Surf2
Frac
Alanine
Ala
A
67
11.5
0.0
6.0
1.8
113
0.74
Arginine
Arg
R
148
14.3
52.0
10.8
-4.5
241
0.64
Asparagine
Asn
N
96
12.3
3.4
5.4
-3.5
158
0.63
Aspartic
Asp
D
91
11.7
49.7
2.8
-3.5
151
0.62
Cysteine
Cys
C
86
13.5
1.5
5.1
2.5
140
0.91
Glutamine
Gln
Q
114
14.5
3.5
5.7
-3.5
189
0.62
Glu. Acid
Glu
E
109
13.6
49.9
3.2
-3.5
183
0.62
Glycine
Gly
G
48
3.4
0.0
6.0
-0.4
85
0.72
Histidine
His
H
118
13.7
51.6
7.6
-3.2
194
0.78
Isoleucine
Ile
I
124
21.4
0.1
6.0
4.5
182
0.88
Leucine
Leu
L
124
21.4
0.1
6.0
3.8
180
0.85
Lysine
Lys
K
135
13.7
49.5
9.7
-3.9
211
0.52
Methionine
Met
M
124
16.3
1.4
5.7
1.9
204
0.85
Phenyl.
Phe
F
135
10.8
0.4
5.5
2.9
218
0.88
Proline
Prot
P
90
17.4
1.6
6.3
-1.6
143
0.64
Serine
Ser
S
73
9.5
1.7
5.7
-0.8
122
0.66
Threonine
Thr
T
93
15.8
1.7
5.7
-0.7
146
0.70
Tryptophan
Trp
W
163
21.7
2.1
5.9
-0.9
259
0.85
Tyrosine
Thr
Y
141
18.0
1.6
5.7
-1.3
229
0.76
Valine
Val
V
105
21.6
0.1
6.0
4.2
160
0.86
109
15.4
13.6
6.0
-0.5
175
0.74
Mean