Martini 3 Coarse‐Grained Force Field: Small Molecules

Abstract

The recent re‐parametrization of the Martini coarse‐grained force field, Martini 3, improved the accuracy of the model in predicting molecular packing and interactions in molecular dynamics simulations. Here, we describe how small molecules can be accurately parametrized within the Martini 3 framework and present a database of validated small molecule models. We pay particular attention to the description of aliphatic and aromatic ring‐like structures, which are ubiquitous in small molecules such as solvents and drugs or in building blocks constituting macromolecules such as proteins and synthetic polymers. In Martini 3, ring‐like structures are described by models that use higher resolution coarse‐grained particles (small and tiny particles). As such, the present database constitutes one of the cornerstones of the calibration of the new Martini 3 small and tiny particle sizes. The models show excellent partitioning behavior and solvent properties. Miscibility trends between different bulk phases are also captured, completing the set of thermodynamic properties considered during the parametrization. We also show how the new bead sizes allow for a good representation of molecular volume, which translates into better structural properties such as stacking distances. We further present design strategies to build Martini 3 models for small molecules of increased complexity.

Modelling structural properties of cyanine dye nanotubes at coarse-grained level

“…The benzimidazole rings are mapped with 4 tiny beads and 1 virtual site at their centre of geometry, following the suggested mapping of small ring-containing molecules with Martini 3. 45 Additionally, there is a dummy particle (black sphere) that does not interact with other beads, but it allows the definition of the axis (dashed line) around which the benzimidazole ring is able to rotate. The substituents of the aromatic core are mostly represented by small beads, as commonly used for chemical fragments consisting of three heavy atoms or four heavy atoms in a branched configuration.…”

“…Martini 3 offers a wide variety of bead types covering a vast number of chemical groups. 26,45 The selection of the bead types for the aromatic core of the cyanine dyes and each substituent is shown in Fig. 3a.…”

Martini 3 coarse-grained force field for poly(para-phenylene ethynylene)s

“…especially aromatic rings as in the case of PPE), higher resolution mapping is recommended, where three or two heavy atoms plus the associated hydrogens are substituted by one small or tiny bead. 28,34 For PPEs, we followed the standardized bottom-up top-down Martini philosophy and defined four tiny beads as our main building block (Fig. 2A).…”

“…33,53 If not stated otherwise, we selected the common Martini 3 MD parameter set from the Martini webportal (https:// www.cgmartini.nl) 54 for the equilibration and production run simulations. 29,34,55 2.2.1 Coarse-grained single and multiple chains. The parameterisation of the bonded potentials between the CG beads was derived from a single chain in solution simulation.…”

“…[30][31][32][33] Martini 3 is based on reparameterised small and tiny beads with improved solutesolvent interactions to better reproduce stacking properties, like the bulk density and the oil-water partitioning behavior. 34 The force field offers the advantage of capturing larger spatiotemporal scales of molecular systems while adjusting the level of resolution of their molecular components. In particular, Martini 3 is very suitable to model long PPE chains, and even mixtures of them, while still taking the essential chemical details of the aromatic rings and the triple bond, giving rise to the enhanced chain stiffness, into account.…”