Extending the Martini 3 Coarse-Grained Force Field to Carbohydrates

Abstract

Carbohydrates play an essential role in a large number of chemical and biochemical processes. High structural diversity and conformational heterogeneity make it problematic to link their measurable properties to molecular features. Molecular dynamics simulations carried out at the level of classical force fields are routinely applied to study the complex processes occurring in carbohydrate-containing systems, while the usefulness of such simulations relies on the accuracy of the underlying theoretical model. In this article, we present the coarse-grained force field dedicated to glucopyranose-based carbohydrates and compatible with the recent version of the Martini force field (v. 3.0). The parameterization was based on optimizing bonded and nonbonded parameters with a reference to the all-atom simulation results and the experimental data. Application of the newly developed coarse-grained carbohydrate model to oligosaccharides curdlan and cellulose displays spontaneous formation of aggregates of experimentally identified features. In contact with other biomolecules, the model is capable of recovering the protective effect of glucose monosaccharides on a lipid bilayer and correctly identifying the binding pockets in carbohydrate-binding proteins. The features of the newly proposed model make it an excellent candidate for further extensions, aimed at modeling more complex, functionalized, and biologically relevant carbohydrates.

Martini-3 Coarse-Grained Models for the Bacterial Lipopolysaccharide Outer Membrane of Escherichia coli

“…In addition, a massless bead is positioned at the geometric center of the sugar ring. This virtual interaction site is assigned a bead type TC4 in the Martini-3 force field to provide sufficient hydrophobicity to stabilize ring stacking interactions with aromatic compounds. , Although a substantially different approach for fragmenting the carbohydrates do exists in literature, our CG mapping scheme for sugar rings is in accordance with a recent work on Martini-3 force field for carbohydrates …”

Approaches and Perspective of Coarse-Grained Modeling and Simulation for Polymer–Nanoparticle Hybrid Systems

“…In light of the underlying chemical building block principle of the MARTINIFF, it is quite possible to model a variety of multicomponent systems. The MARTINI model enjoyed a remarkable success for modeling of a variety of biomolecular processes and has been incorporated by the worldwide user community to study a large number of systems including lipid membrane, protein, sugar, DNA, RNA, hydrocarbons, short peptides, polymers, etc. ,,− ,− , − In the past decade, the MARTINI model has been used successfully to simulate a variety of polymeric systems including homogeneous polymers, e.g., polyethylene (PE), polypropylene (PP), polyethylene glycol (PEO), and polystyrene (PS) . MARTINI CG parameters (bonded and nonbonded) for polymers typically are constructed by matching bond and angle distributions obtained from reference all-atom simulations, the free energy of transfer of the target repeating units in organic and aqueous phases, and long-range structural properties such as radii of gyration. ,, Apart from that, polymer melt density profile, structure factor, end-to-end distance, and persistence length can also be used as the validation target.…”

“…Another popular approach, based on reproduction of energetics, is the MARTINI model. , The MARTINI model, a thermodynamics-based CG model, was initially developed to speed up the biomolecular simulations ,− and later found a growing number of applications in a diverse field of materials science. − The MARTINI coarse-graining approach uses a combination of top-down and bottom-up strategies to determine the CG parameters for different chemical materials (such as lipids, , protein, , DNA, sugars, , polymer, ,,, organic and inorganic nanoparticles, ,, etc.) and form an appropriate bridge between atomistic and macroscopic scales.…”

Martini 3 Coarse-Grained Force Field for Cholesterol

“…Alongside the new bead types and sizes, the model also introduced new guidelines for the parametrization of new molecules that resulted in the need to update and improve many of the previously modeled biomolecules. At the moment, only proteins, common phospholipids, phosphoinositides, some glycolipids, carbohydrates, , small molecules, and green solvents , have been included in the Martini 3 database . The general Martini 2 shortcomings also affected cholesterol, which was excessively lipophilic .…”