Selectivity and transport in aquaporins from molecular simulation studies

The transport of water through aquaporins is a dynamic process that involves rapid movement of a chain of water molecules through the pore of the aquaporin. Structures of aquaporins solved using X-ray crystallography have provided some insights into how water is transported through these channels, and how certain structural features of the pore might help exclude other solutes from passing through the pore. However, such techniques provide only a static picture, and a dynamic picture of the transport and selectivity mechanism at work in aquaporins is possible with molecular dynamics (MD) simulations. In MD simulations, the forces between the different atoms in a system are computed, and the atoms are then allowed to move under the influence of these forces. This allows the sampling of different conformations of the molecule being studied, including conformations that are crucial in driving biological phenomena like water transport. Simulation studies have provided insights into a number of aspects of aquaporins, including the role of the asparagine-proline-alanine (NPA) motif and the aromatic/arginine (ar/R) constriction, water transport mechanism, mechanisms defining the selectivity of the channel, interaction with lipids, response to external electric field, and binding of putative drug molecules. This chapter provides a brief review of the current status of computational modeling of aquaporins using MD simulations. Initially, a brief account of force fields and MD simulations is presented followed by an account of how MD simulations have contributed to further our understanding of different aspects of aquaporins.