Theoretical molecular dynamics simulation of the DIF-1 receptor activation

Abstract

The structure prediction of Dictyostelium Histidine Kinase M (DhkM), a candidate for the receptor of differentiation inducing factor-1 (DIF-1), was carried out and the structural determination and refinement were performed with one hundred nanoseconds molecular dynamics (MD) simulations. Three simulations with different initial velocities generated by pseudo-random number seeds were performed to ensure the accuracy of our simulations and almost the same results were obtained. Docking simulations were executed employing the receptor-structures from the very early stage of the MD simulations. The obtained result exhibited that there is a very high possibility that DhkM could be the receptor of DIF-1. The residues in the core part which are adjacent to Leu111, Asp115, Arg150, Val151, Tyr351 and Val354 play a significant role in ligand binding mechanism. Furthermore, the binding energy was also estimated from free energy analysis for verification. The docking simulations for DIF-2 and DIF-3, which have molecular structures similar to DIF-1 have been explored as well. DIF-3 was especially found to have very low capacity of binding/no docking-simulation which was consistent with experimental data, and two chloro groups of DIF-1 could lead to a transition to a multicellular slug.