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 (available at https://github.com/ricalessandri/ Martini3-small-molecules and http://cgmartini.nl). 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. The present database, along with the outlined design strategies and the modularity of the Martini force field, constitute a resource of models that 1) can be used "as is" in (bio)molecular simulations; 2) gives reference points for the construction of other small molecule models; 3) provides guidelines and reference data for automated topology builders; and 4) can be used as building blocks for the construction of more complex (macro)molecules, hence enabling investigations of complex biomolecular and soft material systems.

Reactive Martini: Chemical Reactions in Coarse-Grained Molecular Dynamics Simulations

“…Matchingly, yellow (B S ) and dark gray (B C ) beads in Figure 2b represent these CG beads, which retain their standard Martini nonbonded interactions (SC6 and TC5, respectively). The orange particle (VS COG ) is a virtual site placed between the two B C beads, as commonly done in connected ring systems in Martini 33 to define angle and dihedral terms and has no nonbonded interactions. The red bead (VS R ) denotes the reactive center as discussed earlier, which interacts with other VS R beads with the V VSd R potential from eq 1.…”

Martini 3 Coarse-Grained Model for Type III Deep Eutectic Solvents: Thermodynamic, Structural, and Extraction Properties

“…Here we only give a cursory account of the parametrization process. A more detailed description of parametrizing small molecules for the Martini 3 force field can be found in the recent work of Alessandri et al…”

A Martini 3 coarse-grain model for the simulation of the photopolymerizable organic phase in dental composites

“…The bead type of bead number 4 was chosen to be TN2a in accordance with methoxybenzene as proposed in ref. 23 . The remaining bead types were selected to be in accordance with the default choice of bead types as presented in ref.…”

“…Note that the bonds between the beads forming the aromatic structure are modelled using constraints as the bond length distribution is narrow. 23 Two different bond lengths were used between type 5 beads. A longer bond length was used between type 5 beads bonded to bead type 4.…”