The simulation approach to bacterial outer membrane proteins.

The outer membrane of Gram-negative bacteria serves as a protective barrier against the external environment but is rendered selectively permeable to nutrients and waste by proteins called porins. Other outer membrane proteins (OMPs) provide the membrane with a variety of other functions including active transport, catalysis, pathogenesis and signal transduction. A relatively small number of crystal or NMR structures of these proteins are known, and it is therefore essential that the maximum possible information be extracted. In this respect, computational techniques enable extrapolation from time- and space-averaged static structures to dynamic, physiological events. Electrostatics approaches have been used to investigate the structures of porins. The stochastic simulation of ion trajectories through these channels has been possible with Brownian dynamics, which treats the membrane and solvent approximately, enabling the prediction of conduction properties. Molecular dynamics has also been applied, enabling fully atomistic descriptions of 'virtual outer membranes'. This has provided atomic resolution descriptions of solute permeation through porins. It has also yielded insights into the dynamics of gating in active transporters and ion channels, as well as providing clues to catalytic mechanisms in outer membrane enzymes. Additionally, simulations are beginning to reveal the common features of interactions between membrane proteins and lipids, with biological implications for OMP folding, stability and mechanism. Future prospects include the simulation of longer, larger and more complex outer membrane systems, with more accurate descriptions of inter-atomic forces.