Scaling Protein–Water Interactions in the Martini 3 Coarse-Grained Force Field to Simulate Transmembrane Helix Dimers in Different Lipid Environments

Martini 3, the latest
version of the widely used Martini force
field for coarse-grained molecular dynamics simulations, is a promising
tool to investigate proteins in phospholipid bilayers. However, simulating
other lipid environments, such as detergent micelles, presents challenges
due to the absence of validated parameters for their constituent molecules.
Here, we propose parameters for the micelle-forming surfactant, dodecylphosphocholine
(DPC). These result in micelle assembly with aggregation numbers in
agreement with the experimental values. However, we identified a lack
of hydrophobic interactions between transmembrane helix protein dimers
and the tails of DPC molecules, preventing insertion and stabilization
of the protein in the micelles. This problem was also observed for
protein insertion by self-assembling 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) or dipalmitoylphosphatidylcholine
(DPPC) bilayers. We propose the reduction of the nonbonded interactions
between protein and water beads by 10% as a simple and effective solution
to this problem that enables protein encapsulation in phospholipid
micelles and bilayers without altering protein dimerization or the
bilayer structure.