Protein contact map
A protein contact map represents the distance between all possible amino acid residue pairs of a three-dimensional protein structure using a binary two-dimensional matrix. For two residues and , the element of the matrix is 1 if the two residues are closer than a predetermined threshold, and 0 otherwise. Various contact definitions have been proposed: The distance between the Cα-Cα atom with threshold 6-12
Overview
Contact maps provide a more reduced representation of a protein structure than its full 3D atomic coordinates. The advantage is that contact maps are invariant to rotations and translations. They are more easily predicted by machine learning methods. It has also been shown that under certain circumstances (e.g. low content of erroneously predicted contacts) it is possible to reconstruct the 3D coordinates of a protein using its contact map.[1][2]
Contact maps are also used for protein
Contact map prediction
With the availability of high numbers of genomic sequences it becomes feasible to analyze such sequences for coevolving residues. The effectiveness of this approach results from the fact that a mutation in position i of a protein is more likely to be associated with a mutation in position j than with a back-mutation in i if both positions are functionally coupled (e.g. by taking part in an enzymatic domain, or by being adjacent in a folded protein, or even by being adjacent in an oligomer of that protein).[4]
Several statistical methods exist to extract from a
Machine learning algorithms have been able to enhance MSA analysis methods, especially for non-homologous proteins (ie. shallow MSA's).[10]
Predicted contact maps have been used in the prediction of
HB Plot
Knowledge of the relationship between a
HB plot offers a simple way of analyzing protein
Features
The plot distinguishes between main chain-main chain, main chain-
Secondary structure elements in HB plot
In representations of the HB plot, characteristic patterns of
- Helicescan be identified as strips directly adjacent to the diagonal.
- Antiparallel beta sheets appear in HB plot as cross-diagonal.
- Parallel beta sheets appears in the HB plot as parallel to the diagonal.
- beta-sheetmotifs.
Examples of usage
Cytochrome P450s
The
Examining the HB plot of the closed and open state of CYP2B4 revealed that the rearrangement of tertiary hydrogen bonds was in excellent agreement with the current knowledge of the cytochrome P450 catalytic cycle.
The first step in
The second step is the transfer of the first electron from
In the third step, oxygen enters CYP2B4 in the closed state - the state where newly formed hydrogen bonds S176-T300, H172-S304, N167-R308 open a tunnel which is exactly the size and shape of an oxygen molecule.
Lipocalin family
The
The overall shape of beta-lactoglobulin is characteristic of the lipocalin family.[
In the three-dimensional structure, tertiary hydrogen bonds are formed (1) near to the entrance, directly involved in conformational rearrangement during ligand binding; and (2) at the bottom of the "barrel". HB plots of the open and closed forms of beta-lactoglobulin are very similar, all unique motifs can be recognized in both forms. Difference in HB plots of open and ligand-bound form show few important individual changes in tertiary hydrogen bonding pattern. Especially, the formation of hydrogen bonds between Y20-E157 and S21-H161 in closed form might be crucial in conformational rearrangement. These hydrogen bonds lie at the bottom of the cavity, which suggests that the closure of the entrance of a lipocalin starts when a ligand reached the bottom of the cavity and broke hydrogen bonds R123-Y99, R123-T18, and V41-Q120. Lipocalins are known to have very low sequence similarity with high structural similarity.[citation needed] The only conserved regions are exactly the region around 20 and 160 with an unknown role.
See also
- Ramachandran plot
- Circuit topology
- Structural classification of proteins
- CATH
- HB plot
- Dot plot (bioinformatics)
- Self-similarity matrix
References
External links
- DISTILL— prediction of protein structural features (including protein residue contact maps)
- Structural Proteomics Tools — includes amino acid contact maps
- ProfCon — prediction of inter-residue contacts
- TMHcon — prediction of helix-helix contacts specifically within the transmembrane parts of membrane proteins
- TMhit — A new transmembrane helix-helix interaction prediction method based on residue contacts[dead link]
- CMAPpro — A protein contact map prediction server
- [1] —A Tool for Protein Contact-Map Visualization in jerseysforcheapshop