Evaluating the Efficiency of the Martini Force Field to Study Protein Dimerization in Aqueous and Membrane Environments

<div> <div> <div> <p>Ionic liquids (IL) are remarkable green solvents, which find applications in many areas of nano- and biotechnology including extraction and purification of value-added compounds or fine chemicals. These liquid salts possess versatile solvation properties that can be tuned by modifications in the cation or anion structure. So far, in contrast to the great success of theoretical and computational methodologies applied to other fields, only a few IL models have been able to bring insights towards the rational design of such solvents. In this work, we develop coarse-grained (CG) models for imidazolium-based ILs using a new version of the Martini force field. The model is able to reproduce the main structural properties of pure ILs, including spatial heterogeneity and global densities over a wide range of temperatures. More importantly, given the high intermolecular compatibility of the Martini force field, this new IL CG model opens the possibility of large-scale simulations of liquid-liquid extraction experiments. As examples, we show two applications, namely the extraction of aromatic molecules from a petroleum oil model and the extraction of omega-3 polyunsaturated fatty acids from a fish oil model. In semi-quantitative agreement with the experiments, we show how the extraction capacity and selectivity of the IL could be affected by the cation chain length or addition of co-solvents. </p> </div> </div> </div>

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Coarse-grained Simulation of Anionic Surfactant Sodium Dodecyl Sulfate

10.21203/rs.3.rs-136348/v1 ◽

2021 ◽

Author(s):

Xiang-feng Jia ◽

Jing-fei Chen ◽

Hui-xue Ren ◽

Qi Wang ◽

Wen Xu ◽

...

Keyword(s):

Force Field ◽

Sodium Dodecyl ◽

Coarse Grained ◽

Inversion Method ◽

Ionic Surfactant ◽

Coarse Grained Model ◽

Piecewise Function ◽

Martini Force Field ◽

Improved Model ◽

Vdw Interaction

Abstract Through analyzing the deficiency of the current coarse-grained (CG) model, a new CG model for the ionic surfactant was proposed based on the Martini force field and iterative Boltzmann inversion method. In this model, the electrostatic interaction can be tackled by using a self-defined piecewise function to avoid the disadvantage of using coarse-grained solvents, and the VDW interaction parameters were derived by iterative methods. Using the improved model, the radial distribution function of NaCl and SDS solution in all-atom OPLS can be completely reproduced. The successful setup of the new coarse-grained model provides a good example of the construction of a high-precision coarse-grained force field.

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Evaluating the Efficiency of the Martini Force Field to Study Protein Dimerization in Aqueous and Membrane Environments

10.26434/chemrxiv.14479872 ◽

2021 ◽

Author(s):

Christos Lamprakis ◽

Ioannis Andreadelis ◽

John Manchester ◽

Camilo Velez-Vega ◽

José S. Duca ◽

...

Keyword(s):

Free Energy ◽

Membrane Proteins ◽

Force Field ◽

Biological Activities ◽

Coarse Grained ◽

Protein Oligomerization ◽

Free Energy Surface ◽

Collective Variables ◽

Protein Dimerization ◽

Dimerization Process

<p>Protein-protein complex assembly is one of the major drivers of biological response. Understanding the mechanisms of protein oligomerization/dimerization would allow one to elucidate how these complexes participate in biological activities and could ultimately lead to new approaches in designing novel therapeutic agents. However, determining the exact association pathways and structures of such complexes remains a challenge. Here, we use parallel tempering metadynamics simulations in the well-tempered ensemble to evaluate the performance of Martini 2.2P and Martini open-beta 3 (Martini 3) force fields in reproducing the structure and energetics of the dimerization process of membrane proteins and proteins in an aqueous solution in reasonable accuracy and throughput. We find that Martini 2.2P systematically overestimates the free energy of association by estimating large barriers in distinct areas, which likely leads to overaggregation when multiple monomers are present. In comparison, the less viscous Martini 3 results in a systematic underestimation of the free energy of association for proteins in solution, while it performs well in describing the association of membrane proteins. In all cases the near-native dimer complexes are identified as minima in the free energy surface albeit not always as the lowest minima. In the case of Martini 3 we find that the spurious supramolecular protein aggregation present in Martini 2.2P multimer simulations is alleviated and thus this force field may be more suitable for the study of protein oligomerization. We propose that the use of enhanced sampling simulations with a refined coarse-grained force field and appropriately defined collective variables is a robust approach for studying the protein dimerization process, although one should be cautious of the ranking of energy minima.</p>

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