The amino acids

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Transcript The amino acids

Bioinformatica I
The amino acids
Things to do today
• Proteins (high speed sneak preview)
– Primary structure
– Secondary structure
– Tertiary structure
• The amino acids
– One amino acid
– Our first protein
– A closer look at the amino acids
– Secondary structure preferences
Our goal for today:
a different view on proteins
Protein?
Protein!
Proteins
• Primary structure
– A.K.A. “the sequence”
• Secondary structure
– Short stretches form distinct ‘substructures’
• Helices
• Strands
• Turns & Loops
• Tertiary structure
– The arrangement of secondary structure elements with
respect to each other
Primary structure
The amino acid sequence (also called primary structure) of a protein is
the order of the amino acids in the protein chain.
The sequence is always read from the
the protein.
to the C-terminus of
For example:
-Lys-Val-Phe-Ala-Met-Cys-Leu-Leu-Arg-Val-COO-
Or (in one-lettercode):
VFAMCLLRV
Proteins
• Primary structure
– A.K.A. “the sequence”
• Secondary structure
– Short stretches form distinct ‘substructures’
• Helices
• Strands
• Turns & Loops
• Tertiary structure
– The arrangement of secondary structure elements with
respect to each other
Secondary structure - helix
Secondary structure - strands
Secondary structure - turn
Proteins
• Primary structure
– A.K.A. “the sequence”
• Secondary structure
– Short stretches form distinct ‘substructures’
• Helices
• Strands
• Turns & Loops
• Tertiary structure
– The arrangement of secondary structure elements with respect to
each other
From sequence to structure?
“When you understand the amino acids, you
understand everything”
The amino acids
A short introduction
One amino acid
- Cα is at the heart of the amino acid
- Cα, C N and O are called backbone atoms
- R can be any of the 20 side chains
Our first protein
Our first protein
• We now have an oligomer
• Proteins are made up
from 20 different amino acids
• String of amino acids is called
“primary structure”
The 20 amino acids
A
C
D
E
F
G
H
I
K
L
M
N
P
Q
R
S
T
V
W
Y
Ala
Cys
Asp
Glu
Phe
Gly
His
Ile
Lys
Leu
Met
Asn
Pro
Gln
Arg
Ser
Thr
Val
Trp
Tyr
Alanine
Cysteine
Aspartic acid (Aspartate)
Glutamic acid (Glutamate)
Phenylalanine
Glycine
Histidine
Isoleucine
Lysine
Leucine
Methionine
Asparagine
Proline
Glutamine
Arginine
Serine
Threonine
Valine
Tryptophan
Tyrosine
The 20 amino acids
The side chains, R, determine the differences in the structural and chemical
properties of the 20 ‘natural’ amino acids.
The 20 amino acids can, for example, be classified as follows:
Hydrophobic
Aliphatic
Aromatic
Ala, Leu, Ile, Val
Phe, Tyr, Trp, (His)
Hydrophilic
Polar
Alcoholic
Charged
Asn, Gln
Ser, Thr, (Tyr)
Arg, Lys, Asp, Glu, (His)
Inbetween:
Sulfur-containing
Special
Met, Cys
Gly (no R), Pro (cyclic)
Several amino acids belong in more than one category.
•There are many ways to characterize the properties of amino acids. The ones
most useful and most commonly used are:
•Hydrophobicity
•Size
•Charge
•Secondary structure preference
•Alcoholicity
•Aromaticity
•And on top of that there are some special characteristics like bridge forming
by cysteines, rigidity of prolines, titrating at physiological pH of histidine,
flexibility of glycines, etc.
Hydrophobic
Aromatic
Hydrophilic - neutral
Hydrophilic - charged
Sulfur - containing
Really special
Cysteines are extra special
Key points about the character of amino acid
side chains
• amino acids don’t fall neatly into classes--they are
different combinations of small/large,
charged/uncharged, polar/nonpolar properties
• the properties of a residue type can also vary with
conditions/environment
Obviously, there are relations between the
physico-chemical characteristics of the amino
acids and their secondary structure
preference.
Secondary structure preferences
Secondary structure - helix
Secondary structure - helix
•
Helices pack because of the hydrogen bonds and because of the hydrophobic
packing of side chains along the length of the helix.
•
Certain residues do this hydrophobic packing better than others, and those
residues are thus good for a helix.
Remember: AMELK
Secondary structure - strands
Secondary structure - strands
•
Also strands pack because hydrophobic packing of side chains along the length of
the strand.
•
Certain residues do this hydrophobic packing better than others, and those
residues are thus good for a strands. b-branched residues (Ile, Thr, Val) are very
good for strands, and so are the large hydrophobic residues.
•
Remember: VITWYF
Secondary structure - turn
Secondary structure - turns
•
To create a turn the backbone needs to be bent pretty sharply, and some residues
are really good at that.
•
Glycine is special because it is so flexible, so it can easily make the sharp turns and
bends needed in a b-turn. Proline is special because it is so rigid; you could say
that it is pre-bent for the turn. Aspartic acid, asparagine, and serine have in
common that they have short side chains that can form hydrogen bonds with the
own backbone. These hydrogen bonds compensate the energy loss caused by
bending the chain into a
•
Remember: PSDNG
A common theme
• Most secondary structure elements are
located at the surface of the protein
• For helices and strands that means that there
is a part facing the ‘outside’ and a part that’s
facing the ‘inside’
What goes where?
Hydrophobicity
Hydrophobicity is the most important characteristic of amino acids. It is the
hydrophobic effect that drives proteins towards folding.
Actually, it is all done by water. Water does not like hydrophobic surfaces. When a
protein folds, exposed hydrophobic side chains get buried, and release water of its sad
duty to sit against the hydrophobic surfaces of these side chains.
Water is very happy in bulk water because there it has on average 3.6 H-bonds and
about six degrees of freedom.
So, whenever we discuss protein structure, folding, and stability, it is all the entropy of
water, and that is called the hydrophobic effect.
When hydrophobic
objects come together in
water, the number of
unhappy waters go
down, and that is good
for stability.
Free waters are happy
waters.