Mohd Rehan, Andrew M Lynn
Jawaharlal Nehru University, New Delhi, India.
The residue conservation in a multiple alignment of a protein and its homologues indicates the importance of the residue for maintaining the structure and function of the protein. Often, the mutational changes at particular conservation site after the gene duplication leads to functional divergence keeping the native fold of protein conserved. The TIM-barrel fold, as an extreme example, includes oxidoreductases, lyases, hydrolases and isomerases which have evolved with divergent functions within the same fold. These proteins, while within each class contain function-specific signals, share fold-specific signals across the function specific groups. In the present study, a novel scoring method REcontext is developed to rank the critical nature of residue by prioritizing its preference for fold or function based on the two kinds of score in a function based pre-classified family of sequences. The method is validated on the published dataset of Major Facilitator Superfamily (MFS), G-Protein Coupled Receptors (GPCRs) and AGC protein kinases with known critical residues from the corresponding representative structures. Furthermore, the residues are separated and assigned fold and function specific rank. For comparison with other methods, we have chosen the physico-chemical conservation, Shannon entropy and Relative entropy scores measured for the subfamily as well as for the whole family. Read More …