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- Complete self-consistent assembly of molecules without external input
- Distributions of neutral and ionic species
- Biomembrane permeability (pH dependent)
- Interfaces, e.g., interfacial tension
- Prediction of micelle formation including critical micelle concentrations (CMC)
- Partition coefficients log P(membrane:water) and free energy profiles of micellar and biomembrane systems (e.g., SDS, DMPC, POPC, DPPC)
- Microemulsions, e.g., fish points, equivalent alkyl carbon numbers (EACN)
Microemulsions
Surfactant containing systems such as microemulsions can be handled with BIOVIA COSMOplex, for example, the self-consistent formation of oil, surfactant and water phases in a microemulsion system as simulated with COSMOplex. Even complex fish point diagrams can be calculated by COSMOplex.
Critical micelle concentrations
Critical micelle concentrations can be calculated for pure surfactant compounds, with a good agreement with the experiment, and even mixtures of them.
Interfaces and interfacial tension
Due to its ability to simulate inhomogeneous systems, COSMOplex can also predict the concentration profile at a liquid-liquid interface and even the average orientation of the molecules. The internal pressure profile at the interface directly corresponds to the interfacial energy. By applying an additional correlation function, the interfacial tension between two liquid mixtures can thus be predicted in a straight forward manner. The liquids can be complex and even contain surfactants.
References:
Klamt, A.; Schwöbel, J.; Huniar, U.; Koch, L.; Terzi, S.; Gaudin, T. COSMOplex: Self-Consistent Simulation of Self-Organizing Inhomogeneous Systems Based on COSMO-RS. Phys. Chem. Chem. Phys. 2019, 21 (18), 9225–9238. https://doi.org/10.1039/C9CP01169B (open access).
By combining the chemical potential from COSMO-RS with atomic pressures in a given simulation geometry, the molecules distribute in space until equilibrium is reached.
Systematic calculation of a large number of positions, orientations and conformers results in a probability distribution and hence a free energy profile for the solutes or system components in the micelle, membrane or microemulsion.
For example, a DMPC bilayer are used to calculate phospholipid-water partition coefficients log P(mem:w) of neutral and ionic compounds of different kind. With a RMSE = 0.62 (neutral compounds) and 0.70 (ions) to experimental data, the COSMOmic model gives very good results, without the need to fit parameters to a given training set.
Download selected model membranes and micelles from the Technical University of Hamburg-Harburg
References:
Klamt, A.; Huniar, U.; Spycher, S.; Keldenich, J. COSMOmic: A Mechanistic Approach to the Calculation of Membrane-Water Partition Coefficients and Internal Distributions within Membranes and Micelles. The Journal of Physical Chemistry B 2008, 112 (38), 12148–12157. https://doi.org/10.1021/jp801736k.
Bittermann, K.; Spycher, S.; Endo, S.; Pohler, L.; Huniar, U.; Goss, K.-U.; Klamt, A. Prediction of Phospholipid-Water Partition Coefficients of Ionic Organic Chemicals Using the Mechanistic Model COSMOmic. J. Phys. Chem. B 2014, 118 (51), 14833–14842. https://doi.org/10.1021/jp509348a.
Jakobtorweihen, S.; Zuniga, A. C.; Ingram, T.; Gerlach, T.; Keil, F. J.; Smirnova, I. Predicting Solute Partitioning in Lipid Bilayers: Free Energies and Partition Coefficients from Molecular Dynamics Simulations and COSMOmic. The Journal of Chemical Physics 2014, 141 (4), 045102. https://doi.org/10.1063/1.4890877.
The mechanistic BIOVIA COSMOperm approach makes use of free energy profiles throughout the biomembrane from chemical potentials and local, membrane layer specific diffusion coefficients (e.g., water, polar head groups, alkyl tails).
This model is applicable to neutral compounds, pH dependent protonation states and permanent ions: pH dependence of permeation is taken into account.
Application example: Black lipid membrane
COSMOperm results are compared to gold standard BLM experiments. A DMPC bilayer is used as reference to calculate intrinsic, passive membrane permeation. With R2 = 0.92 and RMSE = 0.62 to experimental data, COSMOperm gives very good results.
Application example: Skin penetration
COSMOplex can simulate the self-assembly of biomembranes consisting of different membrane components, e.g. phospholipids, ceramides, cholesterol etc. It can even include small molecules such as penetration enhancers or potentially toxic molecules. COSMOplex is used to generate the bio-membranes and COSMOperm for diffusion constants, free energies and partitioning coefficients, which are all required for a mechanistic, multi-scale skin penetration model.
References:
Schwöbel, J. A. H.; Klamt, A. Mechanistic Skin Penetration Model by the COSMOperm Method: Routes of Permeation, Vehicle Effects and Skin Variations in the Healthy and Compromised Skin. Computational Toxicology 2019, 11, 50–64. https://doi.org/10.1016/j.comtox.2019.02.004 (open access).
