The mechanism of complex formation between calmodulin and voltage gated calcium channels revealed by molecular dynamics

Calmodulin, a ubiquitous eukaryotic calcium sensor responsible for the regulation of many fundamental cellular processes, is a highly flexible protein and exhibits an unusually wide range of conformations. Furthermore, CaM is known to interact with more than 300 cellular targets. Molecular dynamics (MD) simulation trajectories suggest that EF-hand loops show different magnitudes of flexibility. Therefore, the four EF-hand motifs have different affinities for Ca(2+) ions, which enables CaM to function on wide range of Ca(2+) ion concentrations. EF-hand loops are 2–3 times more flexible in apo CaM whereas least flexible in Ca(2+)/CaM-IQ motif complexes. We report a unique intermediate conformation of Ca(2+)/CaM while transitioning from extended to compact form. We also report the complex formation process between Ca(2+)/CaM and IQ CaM-binding motifs. Our results showed how IQ motif recognise its binding site on the CaM and how CaM transforms from extended to compact form upon binding to IQ motif.