The Mechanism of the Sarco/Endoplasmic Reticulum ATP-Driven Calcium Pump

Benoit Roux, University of Chicago

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Understanding the detailed molecular mechanism of ion pumps has been a long standing problem in membrane protein biophysics. The calcium transporting pump of the sarcoplasmic reticulum of the skeletal muscle cells (sarco/endoplasmic reticulum Ca²⁺-ATPase, SERCA) has been structurally and biochemically characterized in multiple functional states. Two major outstanding issues are the pathways of the ions to and from the transmembrane binding sites and a detailed understanding of the large scale conformational changes among various functionally relevant states. We will apply all-atom molecular dynamics (MD) and the string method with swarms-of-trajectories to calculate transition pathways among several experimental structures. This study will reveal the molecular mechanisms of important steps in the ion pumping process of a P-type ATPase and will provide a solid ground to understand other ATP-driven ion pumps.