Sarcoplasmic reticulum Ca2+-ATPase (SERCA) is structurally and functionally one of the best studies ion pumps (P-type ATPases). The structural studies have shown that it takes large-scale conformational changes in the cytoplasmic domains, which are coupled with the gating motions in the transmembrane domains for binding/releasing Ca2+. These large motions allow the active transport of Ca2+ across the membrane against the large concentration gradient. To understand the structure-function-dynamics relationship more clearly, we need the structural information of the intermediates between the two crystal structures in the physiological conditions. In the study, we utilize all-atom molecular dynamics (MD) simulations combined with the string method and the free-energy calculations. The transition from E1P to E2P states of SERCA is selected for our MD simulations to examine the order of local conformational changes and the coupling between the conformational changes and the release of Ca2+ toward the cytoplasm. The simulations suggest that the Ca2+-release happens almost at the final stages of the conformational transitions and the simulation results are overall consistent with the previous biochemical experiments.

Conformational changes between E1P to E2P states of SERCA by MD simulations based on string method and free-energy calculations

256th National Meeting (2018)

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