Structure study and predict the function of the diphtheria toxin in different pH levels (Acidic-Basic-Natural) using molecular dynamics simulations

Conformational switching is broadly defined as an alteration in the spatial organization of a macromolecule in response to environmental change. This study was performed to establish the relationship between variable pH and structural and functional aspect of the diphtheria toxin (DT). Molecular dynamics (MD) simulations were performed at different pH levels (4, 6.5, and 10) consist of a DT structure in water at 300K and salt concentration 0.25M at 100ns timescale simulation. Results showed that fluctuations were changed in the key residues at different pH levels. Fluctuations were more profound in the fragments A and B of DT at pH4 compared with pH6.5 and pH10. Fluctuations in the fragment A of DT (DTA) were obtained at pH4 including residues Ser9, Pro25, Tyr46, Leu73, Arg173, and Ala187. The average of the radius of gyration (Rg) and the root mean square deviation (RMSD) of the DT structure showed that decreased at pH 6.5 in comparison with pH4 and pH10. Results showed conformational changes of DT structure at pH4 compared with pH6.5 and pH10.

Keywords: Chain B of Diphtheria Toxin; Chain A of Diphtheria Toxin; Molecular dynamics simulation; Root mean square fluctuation; Variable pH;

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