New methods to measure residues coevolution in proteins
1 School of Mathematical Sciences, Dalian University of Technology, 116024 Dalian, People's Republic of China
2 College of Advanced Science and Technology, Dalian University of Technology, 116024 Dalian, People's Republic of China
3 MPI-CAS Institute of Computational Biology, Chinese Academy of Sciences at Shanghai, 200031 Shanghai, People's Republic of China
4 Scientific Computing Key Laboratory of Shanghai Universities, 200234 Shanghai, People's Republic of China
5 Department of Mathematics, Shanghai Normal University, 200234 Shanghai, People's Republic of China
BMC Bioinformatics 2011, 12:206 doi:10.1186/1471-2105-12-206Published: 26 May 2011
The covariation of two sites in a protein is often used as the degree of their coevolution. To quantify the covariation many methods have been developed and most of them are based on residues position-specific frequencies by using the mutual information (MI) model.
In the paper, we proposed several new measures to incorporate new biological constraints in quantifying the covariation. The first measure is the mutual information with the amino acid background distribution (MIB), which incorporates the amino acid background distribution into the marginal distribution of the MI model. The modification is made to remove the effect of amino acid evolutionary pressure in measuring covariation. The second measure is the mutual information of residues physicochemical properties (MIP), which is used to measure the covariation of physicochemical properties of two sites. The third measure called MIBP is proposed by applying residues physicochemical properties into the MIB model. Moreover, scores of our new measures are applied to a robust indicator conn(k) in finding the covariation signal of each site.
We find that incorporating amino acid background distribution is effective in removing the effect of evolutionary pressure of amino acids. Thus the MIB measure describes more biological background information for the coevolution of residues. Besides, our analysis also reveals that the covariation of physicochemical properties is a new aspect of coevolution information.