Temporal and steric analysis of ionic permeation and binding in SERCA via molecular dynamic simulations.

The availability of the crystal structure of the sarco(endo)plasmic reticulum calcium ATPase (SERCA) has allowed atomic-level molecular dynamic (MD) simulations of this membrane transport protein to be done. The biomedical and nanotechnological implications of this work are discussed as well as the methods of performing the simulations and analysis. We have performed nanosecond timescale simulations of SERCA for several of its known conformations in a lipid/water environment. One simulation contained Ca(2+) ions, while others without ions were analyzed by techniques such as steric pathway determination. We discuss details of the resulting putative cytoplasmic and lumenal pathways, along with experimental evidence from the literature to support our conclusions. Finally, we give a brief overview of future research directions, as they pertain to MD simulations and their analysis. The methodology used in this work shows that significant insight into the structure-function relationship of ion-motive transmembrane pumps can be derived by a combination of simulation tools and analysis techniques including MD trajectories, steric analysis and electrostatic potentials.