Molecular Modeling of Triton X Micelles: Force Field Parameters, Self-Assembly, and Partition Equilibria

Abstract

Nonionic surfactants of the Triton X-series find various applications in extraction processes and as solubilizing agents for the purification of membrane proteins. However, so far no optimized parameters are available to perform molecular simulations with a biomolecular force field. Therefore, we have determined the first optimized set of CHARMM parameters for the Triton X-series, enabling all-atom molecular dynamics (MD) simulations. In order to validate the new parameters, micellar sizes (aggregation numbers) of Triton X-114 and Triton X-100 have been investigated as a function of temperature and surfactant concentration. These results are comparable with experimental results. Furthermore, we have introduced a new algorithm to obtain micelle structures from self-assembly MD simulations for the COSMOmic method. This model allows efficient partition behavior predictions once a representative micelle structure is available. The predicted partition coefficients for the systems Triton X-114/water and Triton X-100/water are in excellent agreement with experimental results. Therefore, this method can be applied as a screening tool to find optimal solute-surfactant combinations or suitable surfactant systems for a specific application.

Shedding light on the puzzle of drug-membrane interactions: Experimental techniques and molecular dynamics simulations

“…COSMOmic was recently optimized for charged solutes, with regards to the membrane dipole potential [181]. COSMOmic has proved its usefulness for the determination of membrane/water partition coefficients for different solutes [77,126,[179][180][181][182][183][184][185][186][187] and for micelle/water partition coefficients [183,[188][189][190][191]. It was also shown that the results of COSMOmic and MD simulations are comparable [126,182].…”

Self-Assembly of Triton X-100 in Water Solutions: A Multiscale Simulation Study Linking Mesoscale to Atomistic Models

“…27 Very recently, an optimized set of CHARMM parameters for the Triton X-series, suitable for atomistic molecular dynamics (MD) simulations, has been 5 presented. 28 Although atomistic simulations provide very detailed models of surfactants, they are highly computationally expensive techniques for studying the assembling processes involving nanostructures occurring on the mesoscopic time and length scales. Indeed, the assembly process of surfactants can be obtained only in some cases from a random mixture of surfactants in aqueous solution within atomic resolution with reasonable simulation time.…”

Pressure effect on micellization of non-ionic surfactant Triton X-100

“…Thus, aggregates with ε = 0 correspond to a highly symmetrical shape with spherical geometry, while values different from zero indicate drifts to a more elliptical shape. 23,42,43 By monitoring the variation of ε over the simulation time, we conclude that the aggregate cannot be considered entirely spherical but resembling a spheroid (ε = 0.15-0.3). ε values correlate well with the variations of the radius of gyration (Rg) on the principal axes of the micelle [Fig.…”

“…By assuming that the micelle adopts a spherical shape under high pressures, the Rg can be calculated as the Thus, the radius of the micelle, Rs, can be calculated from the relation to Rg according to 23,43 Rs = 5 3 Rg.…”

“…1 Currently, there is a deficiency in the literature on the effect of high pressure on non-ionic surfactants at the molecular level. At present, few models of Triton X-100 are reported in the literature [22][23][24][25] and only two articles can be found concerning the self-assembly of Triton X-100 micelles as a function of temperature and surfactant concentration using computational methodologies. These studies were carried out using all-atom MD simulations 23 and coarse-grained (CG) model with reverse mapping, 22 obtaining an atomistic model of the micellar clusters from mesoscale simulations.…”