Molecular dynamics simulations of barley and maize lipid transfer proteins show different ligand binding preferences in agreement with experimental data.

Experimental studies of barley and maize lipid transfer proteins (LTPs) show that the two proteins bind the ligand palmitate in opposite orientations in their internal cavities. Moreover, maize LTP is reported to bind the ligand caprate in the internal cavity in a mixture of two orientations with approximately equal occupancy. Six 30 ns molecular dynamics (MD) simulations of maize and barley LTP with ligands bound in two orientations (modes M and B) have been used to understand the different ligand binding preferences. The simulations show that both maize and barley LTP could bind palmitate in the orientation observed experimentally for maize LTP (mode M), with the predominant interaction being a salt bridge between the ligand carboxylate headgroup and a conserved arginine side chain. However, the simulation of barley LTP with palmitate in the mode B orientation shows the most favorable protein-ligand interaction energy. In contrast, the simulations of maize LTP with palmitate and with caprate in the mode B orientation show no persistent ligand binding, the ligands leaving the cavity during the simulations. Sequence differences between maize and barley LTP in the AB loop region, in residues at the base of the hydrophobic cavity, and in the helix A region are identified as contributing to the different behavior. The simulations reproduce well the experimentally observed binding preferences for palmitate and suggest that the experimental data for maize LTP with caprate reflect ligand mobility in binding mode M rather than the population of binding modes M and B.