Molecular dynamics simulations of membrane channels and transporters

Abstract

Membrane transport constitutes one of the most fundamental processes in all living cells with proteins as major players. Proteins as channels provide highly selective diffusive pathways gated by environmental factors, and as transporters furnish directed, energetically uphill transport consuming energy. X-ray crystallography of channels and transporters furnishes a rapidly growing number of atomic resolution structures, permitting molecular dynamics (MD) simulations to reveal the physical mechanisms underlying channel and transporter function. Ever increasing computational power today permits simulations stretching up to 1 micros, that is, to physiologically relevant time scales. Membrane protein simulations presently focus on ion channels, on aquaporins, on protein-conducting channels, as well as on various transporters. In this review we summarize recent developments in this rapidly evolving field.

Figure 1

Membrane channels studied recently. Proteins are shown in cartoon representation, with the lipid bilayer in the background. The protein subunits are colored differently, and the dominant permeating molecules are indicated in the case of each channel.

Figure 2

Simulations of AQP0-mediated membrane junction (9). Cross-section of an AQP0 octamer embedded in a double lipid bilayer. Two pairs of interlocked AQP0 monomers that connect the two cells are shown. Permeating water is red and white. Other waters are shown as a white surface. Figure courtesy of Morten Jensen.

Figure 3

Membrane transporters studied recently. Shown in the same format as in Fig. 1, each transporter is colored according to domain with substrates and direction of transport indicated. These transporters are found in a variety of cellular membranes including the cytoplasmic membrane (e.g., MalEFGK), the bacterial outer membrane (BtuB), and the mitochondrial inner membrane (AAC).

Figure 4

Initial steps in the transport cycle of the glutamate transporter GlT (lower left). Binding of the substrate to the apo state (upper left) induces a focusing of two helical dipoles (middle right) which then permits binding of a Na⁺ ion (lower right) (52). Figure courtesy of Zhijian Huang.