From Prokaryotes to Eukaryotes: Molecular Modeling and Simulation Studies of Ion Channels

This chapter focuses on homology modeling and molecular dynamics (MD) simulations studies of ion channels for the range of single cell organisms from prokaryotes to eukaryotes. The glutamate receptor channels (GluRs) share some distant homology in their transmembrane (TM) domains with K channels but possess distinct extracellular ligand-binding domains for which several structures, of both bacterial and mammalian homologs, are known. It can be seen that molecular modeling and simulations can contribute to studies of ion channels in two respects. Modeling studies enable extrapolation from experimental structures of prokaryotic ion channels to molecular models of eukaryotic homologs, thus aiding design and interpretation of, for example, mutation experiments for dissecting structure-function relationships. Ion channel structures and ion channel models may also be used as the basis of multinanosecond MD simulations. Finally, it will become increasingly important to run multiple simulations on multiple channels to allow comparative analysis of simulation results, which in turn will enable the formulation of more general hypotheses concerning the relationship between the conformational dynamics of channel proteins and their physiological functions.