Chemotaxis of Vibrio cholerae is a complex process where multiple paralogues of various chemotaxis genes participate. V. cholerae contains five copies of the response regulator protein CheY (CheY_V) and the role played by these CheY homologs in chemotaxis and virulence are investigated only through a few in vivo studies. As identification of the molecular features that discriminate CheY_Vs in terms of FliM binding is necessary for the detailed understanding of chemotaxis and pathogenesis, we built the models of CheY_Vs through comparative modeling and MD simulation was performed on each model in their phosphorylated and Mg⁺² bound state. Our analysis identified the key structural elements, unique to CheY3_V, which complement the N-terminal part of FliMV and we explained how the structure, shape, and surface properties of the FliM binding pocket of other CheY_Vs abrogate this function. Furthermore, we have provided the structural basis of a putative cross species interaction between CheY_E and FliM_V, identified in a recent in vivo study.

Key words: Vibrio cholerae; Chemotaxis; FliM binding; Comparative modeling; and MD simulation.