Calculating the Kinetics of Calcium Ions Associating with Calmodulin Using Molecular Dynamics and Brownian Dynamics

Calmodulin is a ubiquitous calcium-sensing protein which activates many downstream cellular processes. Calmodulin cooperatively binds up to four calcium ions which can occupy the four EF-hand motif sites. As more calcium ions bind to calmodulin, this protein becomes more likely to change conformation from the Open/Inactive state to the Closed/Active state. Studying the kinetics of calcium binding to calmodulin can lead to further insight into how the conformational state of calmodulin depends on the local calcium concentration and the effect of cooperative binding due to calcium-induced conformational changes. This project investigates the kinetics of calcium binding to calmodulin binding sites by combining Brownian Dyanmics and Molecular Dynamics to analyze how the presence of calcium ions affects the subsequent binding of additional calcium. Obtaining the kinetic information for these interactions can inform the mechanism for cooperative calcium binding influencing the conformational state of calmodulin.