Download Amino acid properties

Amino Acids
“When you understand the amino acids,
you understand everything”
©CMBI 2006
Residue properties determine the alignment scores
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.
©CMBI 2001
Residue properties determine the alignment scores
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.
©CMBI 2001
HYDROPHOBICITY
©CMBI 2006
Residue properties determine the alignment scores
Aliphatic/hydrophobic
Polar
Alcoholic
Sulfur-containing
Aromatic
Charged
Special
Helix lovers
Strand lovers
Turn lovers
Ala, Leu, Ile, Val
Asn, Gln
Ser, Thr, (Tyr)
Met, Cys
Phe, Tyr, Trp, (His)
Arg, Lys, Asp, Glu, (His)
Gly (no R), Pro (cyclic)
Ala Met Glu Leu Lys (Gln Phe)
Val Ile Thr Trp Tyr Phe
Pro Ser Asp Asn Gly
©CMBI 2006
Secondary Structure Preference
Amino acids form chains, the sequence or primary structure.
These chains fold in -helices, b-strands, b-turns, and loops (or for
short, helix, strand, turn and loop), the secondary structure.
These secondary structure elements fold further to make whole
proteins, but more about that later.
There are relations between the physico-chemical characteristics of
the amino acids and their secondary structure preference. I.e., the
b- branched residues (Ile, Thr, Val) like to sit in b-strands.
©CMBI 2006
β-branched prefers β-strand
©CMBI 2006
Secondary Structure Preferences
Isoleucine
Leucine
Phenylalanine
Threonine
Tryptophan
Tyrosine
Valine
helix
1.08
1.41
1.13
0.83
1.08
0.69
1.06
strand
1.60
1.30
1.38
1.19
1.37
1.47
1.70
turn
0.47
0.59
0.60
0.96
0.96
1.14
0.50
Subset of strand-lovers. These
residues either have in common
their b-branched nature (Ile, Thr,
Val) or their large and hydrophobic
character (rest).
©CMBI 2006
Secondary Structure Preference
Most secondary structure elements are located at the surface of the
protein:
So, most helices have an inward
pointing side, and an outward pointing
side.
©CMBI 2006
Helix
©CMBI 2006
Helix
©CMBI 2006
Helix
©CMBI 2006
Helix
©CMBI 2006
Helix
©CMBI 2006
Helix
©CMBI 2006
Helix
So, helices pack because of the hydrogen bonds and because of
the hydrophobic packing of side chains along the length of the
helix.
Ceratin residues do this hydrophobic packing better than others,
and those residues are thus good for a helix.
©CMBI 2006
Secondary Structure Preferences
Alanine
Glutamic Acid
Glutamine
Leucine
Lysine
Methionine
Phenylalanine
helix
1.42
1.39
1.11
1.41
1.14
1.45
1.13
strand
0.83
1.17
1.10
1.30
0.74
1.05
1.38
turn
0.66
0.74
0.98
0.59
1.01
0.60
0.60
Subset of helix-lovers. If we forget alanine (I don’t understand that
things affair with the helix at all), they share the presence of a
(hydrophobic) C-b, C-g and C-d (S-d in Met). These hydrophobic
atoms pack on top of each other in the helix. That creates a
hydrophobic effect.
©CMBI 2006
Secondary Structure Preferences
©CMBI 2006
Secondary Structure Preferences
Aspartic Acid
Asparagine
Glycine
Proline
Serine
helix
1.01
0.67
0.57
0.57
0.77
strand
0.54
0.89
0.75
0.55
0.75
turn
1.46
1.56
1.56
1.52
1.43
Subset of turn-lovers. 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 prebend for the b-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 b-turn.
©CMBI 2006
Secondary Structure Preferences
Alanine
Arginine
Aspartic Acid
Asparagine
Cysteine
Glutamic Acid
Glutamine
Glycine
Histidine
Isoleucine
Leucine
Lysine
Methionine
Phenylalanine
Proline
Serine
Threonine
Tryptophan
Tyrosine
Valine
helix
1.42
0.98
1.01
0.67
0.70
1.39
1.11
0.57
1.00
1.08
1.41
1.14
1.45
1.13
0.57
0.77
0.83
1.08
0.69
1.06
strand
0.83
0.93
0.54
0.89
1.19
1.17
1.10
0.75
0.87
1.60
1.30
0.74
1.05
1.38
0.55
0.75
1.19
1.37
1.47
1.70
turn
0.66
0.95
1.46
1.56
1.19
0.74
0.98
1.56
0.95
0.47
0.59
1.01
0.60
0.60
1.52
1.43
0.96
0.96
1.14
0.50
©CMBI 2006
Chou Fasman parameters
Say your dataset is 1000 amino acids and 350 of them are in alpha-helix
conformation.
This is 35%.
There are 50 Alanines in your set and 25 of them are in alpha-helix
conformation.
This is 50%.
The helix preference parameter P for Ala is 50/35=1,43
©CMBI 2006
Chou Fasman parameters
Take home message:
Preference parameter > 1.0
 specific residue has a preference for the specific secondary structure.
Preference parameter = 1.0
 specific residue does not have a preference for, nor dislikes the specific
secondary structure
Preference parameter < 1.0
 specific residue dislikes the specific secondary structure.
©CMBI 2006
Sequence Alignment
Don’t forget that we still want to gather information about an
unknown protein for which we determined the sequence.
To gather that information, we will need databases and sequence
alignments.
To do these sequence alignments, we need to know everything
about the amino acids.
And that is what we are working on now.
©CMBI 2006