Temporal and steric analysis of ionic permeation and binding in SERCA via moleculardynamic simulations

Abstract

The availability of the crystal structure of the sarco(endo)plasmic reticulum calciumATPase (SERCA) has allowed atomic-level molecular dynamic (MD) simulations of thismembrane transport protein to be done. The biomedical and nanotechnologicalimplications of this work are discussed as well as the methods of performing the simulationsand analysis. We have performed nanosecond timescale simulations of SERCA for several ofits known conformations in a lipid/water environment. One simulation containedCa2+ ions, while others without ions were analyzed by techniques such as steric pathwaydetermination. We discuss details of the resulting putative cytoplasmic and lumenalpathways, along with experimental evidence from the literature to support ourconclusions. Finally, we give a brief overview of future research directions, as theypertain to MD simulations and their analysis. The methodology used in this workshows that significant insight into the structure–function relationship of ion-motivetransmembrane pumps can be derived by a combination of simulation tools and analysistechniques including MD trajectories, steric analysis and electrostatic potentials.