Triton X-100 (TX-100) is a nonionic surfactant used in the solubilisation of lipid bilayer cell membranes. It is used in the manufacture of split virus vaccines for all strains of influenza, but the dynamics of the rupture of the virion lipid envelope have never been observed. The biology community has in recent years turned to molecular dynamics simulations to analyse this process at the molecular scale. A major obstacle to this is the high computational demand for such a simulation, if atomistic forcefields are used. The MARTINI force field represents one attempt to deal with this by coarse graining such systems, with a 4:1 particle mapping, to allow the simulations to run with diminished computational demand.
MARTINI has been utilised a number of times unsuccessfully in this regard. Therefore it was necessary to determine the validity of the MARTINI force field for this application. Atomistic aggregation dynamics for TX-100 in the lipid bilayer, solvated by water and ions, were used as a validation benchmark for MARTINI simulations. The radial distribution function (RDF), diffusivity and clustering behaviour were used to probe the validity of the MARTINI parametrisation for TX-100.
The RDF and diffusivity calculations revealed that, in MARTINI, the head groups experience a net repulsive effect and therefore no tendency for aggregation - despite evidence of aggregation processes in atomistic simulations. This was attributed to the observation that the TX-100 tails were observed to be anomalously bound to the bilayer interface with both the original and head group modified parameters in MARTINI.
Atomistic simulations showed that the hydrophobic TX-100 head group does not play any role other than as anchoring, while collisions from the water cause the otherwise hydrophilic tails to be hydrophobically driven together.
The TX-100 tail parameters were adjusted in accordance with this proposed hypothesis, which resulted in a successful validation against CHARMM simulations.