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Updated: Jul 11, 2026

Optimization of Synthetic Proteins: Identification of Interpositional Dependencies Indicating Structurally and/or Functionally Linked Residues
Published on: July 14, 2015
Finding coevolving amino acid residues using row and column weighting of mutual information and multi-dimensional
Rodrigo Gouveia-Oliveira1, Anders G Pedersen
1Center for Biological sequence analysis, Technical University of Denmark, Building 208, 2800 Lyngby, Denmark. rodrigo@cbs.dtu.dk
Background:
Some amino acid residues functionally interact with each other. This interaction will result in an evolutionary co-variation between these residues - coevolution. Our goal is to find these coevolving residues.
Results:
We present six new methods for detecting coevolving residues. Among other things, we suggest measures that are variants of Mutual Information, and measures that use a multidimensional representation of each residue in order to capture the physico-chemical similarities between amino acids. We created a benchmarking system, in silico, able to evaluate these methods through a wide range of realistic conditions. Finally, we use the combination of different methods as a way of improving performance.
Conclusion:
Our best method (Row and Column Weighed Mutual Information) has an estimated accuracy increase of 63% over Mutual Information. Furthermore, we show that the combination of different methods is efficient, and that the methods are quite sensitive to the different conditions tested.
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