Automated Coarse-Grained Mapping Algorithm for the Martini Force Field and Benchmarks for Membrane–Water Partitioning

Abstract

With a view to high-throughput simulations, we present an automated system for mapping and parameterizing organic molecules for use with the coarse-grained Martini force field. The method scales to larger molecules and a broader chemical space than existing schemes. The core of the mapping process is a graph-based analysis of the molecule’s bonding network, which has the advantages of being fast, general, and preserving symmetry. The parameterization process pays special attention to coarse-grained beads in aromatic rings. It also includes a method for building efficient and stable frameworks of constraints for molecules with structural rigidity. The performance of the method is tested on a diverse set of 87 neutral organic molecules and the ability of the resulting models to capture octanol–water and membrane–water partition coefficients. In the latter case, we introduce an adaptive method for extracting partition coefficients from free-energy profiles to take into account the interfacial region of the membrane. We also use the models to probe the response of membrane–water partitioning to the cholesterol content of the membrane.

Martini 3 Coarse-Grained Force Field: Small Molecules

“…COG-based (like COM-based) bond lengths can be directly extracted from AA models: such a direct link to the underlying atomistic structure is important, as it, for example, makes them suitable for automated topology building. [12,[25][26][27][28] Hence, using COG-based mapping of atomistic structures constitute the standard procedure for obtaining bonded parameters in Martini 3; such parameters can then, if necessary, be refined, as discussed in more detail in Section 3.2. Aromatic Rings.…”

“…Furthermore, they form an initial set of "rules" which may be implemented in the next generation of programs aimed at automated topology building of Martini models. [12,26,28] Many of the model design strategies outlined below leverage virtual (interaction) sites. [31] In general, the use of virtual sites improves the numerical stability of Martini models of small molecules which are comprised of multiple, or extended, aro-matic structures.…”

“…On the biomolecular side, a natural application of the small molecules presented here combined with the Martini protein models [24] is to investigate protein-ligand interactions in unbiased or biased MD simulations. [21,73] The parametrization guidelines and strategies are expected to facilitate the building of databases with accurate Martini 3 models of small molecules; this possibly will require the help of the next-generation of programs aimed at automated topology building of Martini models, [12,26,28] and automated parametrization of bonded parameters. [25,27] On the materials science side, Martini 3 and the presented parametrization guidelines are expected to open up the possibility of more easily model organic functional materials in general.…”

“…To fully harness the capabilities of Martini 3 CG modeling of (small) molecules, such strategies need to be implemented in the next-generation of programs aimed at automated topology building of Martini models. [12,26,28] In conclusion, we presented how small molecules can be accurately parameterized within the Martini 3 framework, and initiated a database of validated small molecule models. The present database, along with the outlined model 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, Adv.…”

How Ethanolic Disinfectants Disintegrate Coronavirus Model Membranes: A Dissipative Particle Dynamics Simulation Study

“…These ”bounded” ethanol molecules are partly influenced by the membrane, although not completely partitioned into it. Inspired by a recent work, 59 we have adopted a method based on the assumption that any deviations in the Gibbs free energy profiles from the corresponding values in the aqueous phase ( ΔG bulk ≈ 0) must be due to interactions with the membrane. We have partitioned the simulation along the z direction into a number of bins of width 0.305 nm.…”