Principles of Protein Structure,
Comparative Protein Modelling and
Visualisation
Nicolas Guex and Manuel C. Peitsch
GlaxoWellcome Experimental Research S.A.
16, chemin des Aulx
1228 Plan-les-Ouates / Switzerland
,
1 Secondary structure and backbone conformation
1.1 Peptide Torsion Angles
The figure below shows the three main chain torsion angles of a polypeptide. These are phi
(), psi (), and omega (.
The planarity of the peptide bond restricts to 180 degrees in very nearly all of the main chain
peptide bonds. In rare cases = 10 degrees for a cis peptide bond which usually involves
proline.
1.2 The Ramachandran Plot
In a polypeptide the main chain N-C and C-C bonds relatively are free to rotate. These
rotations are represented by the torsion angles phi () and psi (), respectively.
GN Ramachandran used computer models of small polypeptides to systematically vary and
with the objective of finding stable conformations. For each conformation, the structure was
,examined for close contacts between atoms. Atoms were treated as hard spheres with
dimensions corresponding to their van der Waals radii. Therefore, and angles, which cause
spheres to collide correspond to sterically disallowed conformations of the polypeptide
backbone.
In the diagram above the white areas correspond to conformations where atoms in the
polypeptide come closer than the sum of their van der Waals radii. These regions are sterically
disallowed for all amino acids except glycine which is unique in that it lacks a side chain. The
red regions correspond to conformations where there are no steric clashes, i.e. these are the
allowed regions namely the -helical and -sheet conformations. The yellow areas show the
allowed regions if slightly shorter van der Waals radii are used in the calculation, i.e. the
atoms are allowed to come a little closer together. This brings out an additional region which
corresponds to the left-handed -helix.
L-amino acids cannot form extended regions of left-handed helix but occasionally individual
residues adopt this conformation. These residues are usually glycine but can also be
asparagine or aspartate where the side chain forms a hydrogen bond with the main chain and
therefore stabilises this otherwise unfavourable conformation. The 310 helix occurs close to the
upper right of the -helical region and is on the edge of allowed region indicating lower
stability.
Disallowed regions generally involve steric hindrance between the side chain C methylene
group and main chain atoms. Glycine has no side chain and therefore can adopt phi and psi
angles in all four quadrants of the Ramachandran plot. Hence it frequently occurs in turn
regions of proteins where any other residue would be sterically hindered.
,Below is a ramachandran plot of a protein containing almost exclusively beta-strands (yellow
dots) and only one helix (red dots). Note how few residues are out of the allowed regions; and
note also that they are almost all Glycines (depicted with a little square instead of a cross.
Observe the effect of minor Phi and Psi angle changes:
, 1.2 The -helix.
1.2.1 Development of an -helix structure model.
Pauling and Corey twisted models of polypeptides around to find ways of getting the
backbone into regular conformations which would agree with -keratin fibre diffraction data.
The most simple and elegant arrangement is a right-handed spiral conformation known as the
'-helix'.
Comparative Protein Modelling and
Visualisation
Nicolas Guex and Manuel C. Peitsch
GlaxoWellcome Experimental Research S.A.
16, chemin des Aulx
1228 Plan-les-Ouates / Switzerland
,
1 Secondary structure and backbone conformation
1.1 Peptide Torsion Angles
The figure below shows the three main chain torsion angles of a polypeptide. These are phi
(), psi (), and omega (.
The planarity of the peptide bond restricts to 180 degrees in very nearly all of the main chain
peptide bonds. In rare cases = 10 degrees for a cis peptide bond which usually involves
proline.
1.2 The Ramachandran Plot
In a polypeptide the main chain N-C and C-C bonds relatively are free to rotate. These
rotations are represented by the torsion angles phi () and psi (), respectively.
GN Ramachandran used computer models of small polypeptides to systematically vary and
with the objective of finding stable conformations. For each conformation, the structure was
,examined for close contacts between atoms. Atoms were treated as hard spheres with
dimensions corresponding to their van der Waals radii. Therefore, and angles, which cause
spheres to collide correspond to sterically disallowed conformations of the polypeptide
backbone.
In the diagram above the white areas correspond to conformations where atoms in the
polypeptide come closer than the sum of their van der Waals radii. These regions are sterically
disallowed for all amino acids except glycine which is unique in that it lacks a side chain. The
red regions correspond to conformations where there are no steric clashes, i.e. these are the
allowed regions namely the -helical and -sheet conformations. The yellow areas show the
allowed regions if slightly shorter van der Waals radii are used in the calculation, i.e. the
atoms are allowed to come a little closer together. This brings out an additional region which
corresponds to the left-handed -helix.
L-amino acids cannot form extended regions of left-handed helix but occasionally individual
residues adopt this conformation. These residues are usually glycine but can also be
asparagine or aspartate where the side chain forms a hydrogen bond with the main chain and
therefore stabilises this otherwise unfavourable conformation. The 310 helix occurs close to the
upper right of the -helical region and is on the edge of allowed region indicating lower
stability.
Disallowed regions generally involve steric hindrance between the side chain C methylene
group and main chain atoms. Glycine has no side chain and therefore can adopt phi and psi
angles in all four quadrants of the Ramachandran plot. Hence it frequently occurs in turn
regions of proteins where any other residue would be sterically hindered.
,Below is a ramachandran plot of a protein containing almost exclusively beta-strands (yellow
dots) and only one helix (red dots). Note how few residues are out of the allowed regions; and
note also that they are almost all Glycines (depicted with a little square instead of a cross.
Observe the effect of minor Phi and Psi angle changes:
, 1.2 The -helix.
1.2.1 Development of an -helix structure model.
Pauling and Corey twisted models of polypeptides around to find ways of getting the
backbone into regular conformations which would agree with -keratin fibre diffraction data.
The most simple and elegant arrangement is a right-handed spiral conformation known as the
'-helix'.
