Ca2+ dissociation from the C-terminal EF-hand pair in calmodulin: A steered molecular dynamics study

We used steered molecular dynamics (SMD) to simulate the process of Ca2+ dissociation from the EF-hand motifs of the C-terminal lobe of calmodulin. Based on an analysis of the pulling forces, the dissociation sequences and the structural changes, we show that the Ca2+-coordinating residues lose their binding to Ca2+ in a stepwise fashion. The two Ca2+ ions dissociate from the two EF-hands simultaneously, with two distinct groups among the five Ca2+-coordinating residues affecting the EF-hand conformational changes differently. These results provide new insights into the effects of Ca2+ on calmodulin conformation, from which a novel sequential mechanism of Ca2+-calmodulin dissociation is proposed.