May 15, 2007
Using Mutual Information to detect co-evolving amino acids shows promise as a technique to detect protein-protein interactions. This has strong applications in RNA virus with high mutation rates. Dengue Fever is caused by a single-stranded RNA flavivirus. The Genome Institute of Singapore and Novartis Institute of Tropical Diseases has put together a great portal on the Dengue virus. Dengue Portal
Using sequence data for 160 complete genomes of Dengue published at the Dengue Portal the following network graph was created showing potential protein-protein interactions. It is important to understand that the interaction between two amino acids with high mutual information could be positive which would indicate the two amino acids or the protein surface located around those two sequence position have an affinity for each other. This would indicate that the two proteins share an interface. It is also possible that the mutual information relationship between the two amino acids prevents the two protein surfaces from interacting to reserve the protein surface for another protein.
Once the sequence positions of interest have been identified then highlighting those sequence positions on a solved PDB structure can provide additional information about the accuracy or importance of the predicted sequence position. The Major Envelope protein E has a solved structure 1THD as a trimer. The sequence positions in E that have high mutual information are color coded. It is interesting to point out that the sequence positions come from various sections in the sequence but in 3D space form a straight line along the trimer where the center E structure is flipped and rotated 180 degrees. This is an interesting indicator that the line or axis formed by these sequence position may be of important. The other interfaces are at the end of the structure and even though they are distance in sequence positions they are all approximate neighbors in 3D space.
Top scoring 50 MI pairs
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Protein E structure as a trimer where the center E structure is anti-parallel
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