The conserved Arg241-Glu439 salt bridge determines flexibility of the inositol 1,4,5-trisphosphate receptor binding core in the ligand-free state.

Inositol 1,4,5-trisphosphate receptor (InsP3 R) is an intracellular Ca(2+) -release channel activated by binding of inositol 1,4,5-trisphosphate (InsP3 ) to the InsP3 binding core (IBC). Structural change in the IBC upon InsP3 binding is the key process in channel pore opening. In this study, we performed molecular dynamics (MD) simulations of the InsP3 -free form of the IBC, starting with removal of InsP3 from the InsP3 -bound crystal structure, and obtained the structural ensemble of the InsP3 -free form of the IBC.