Integral membrane proteins play many critical roles in biology, including that of transporters. Modeling transporter mechanisms, however, can be difficult in vitro, and in silico simulations of behavior may offer detailed and atomistic insights into how these proteins function. All-atom molecular dynamics simulations of a bacterial integral membrane protein embedded in a phospholipid bilayer reveal delicate interactions occurring between specific residues and constituent bilayer lipids over several replicate simulations. In addition, these simulations reveal potential pathways through which transport cargo may be trafficked, particularly through the presence of water paths throughout the transmembrane region. Such pathways are facilitated by the presence of charged and polar residues located within the typically nonpolar transmembrane region. Hydrogen bonding and ionic interactions between the aqueous solvent and these residues contribute to water movement through the protein, potentially indicating mechanisms for cargo transport. Further characterization of these hydrated transmembrane regions may lend further insight into transport pathways and membrane protein-mediated delivery of cargo.
Jenna O. Mackenroth (Sun,) studied this question.