Martini 3: a general purpose force field for coarse-grained molecular dynamics

Abstract

The coarse-grained Martini force field is widely used in biomolecular simulations. Here, we present the refined model, Martini 3 (http://cgmartini.nl), with an improved interaction balance, new bead types, and expanded ability to include specific interactions representing, e.g. hydrogen bonding and electronic polarizability. The new model allows more accurate predictions of molecular packing and interactions in general, which is exemplified with a vast and diverse set of applications, ranging from oil/water partitioning and miscibility data to complex molecular systems, involving protein-protein and protein-lipid interactions and material science applications as ionic liquids and aedamers.

The Martini Model in Materials Science

“…Recent identification of some of the limits of the current Martini version, [ 6,27 ] opened the way for the development of a new version, coined Martini 3. [ 292 ] This new version's more general re‐parametrization strategy, which did not exclusively include biomolecules, is expected to further boost the application of Martini in soft materials science. Areas in materials science that are particularly expected to benefit from the new re‐parametrization are applications involving: polymers, which constitute the backbone of soft materials science given their high tunability; conjugated molecules, which are ubiquitous in materials given the possibility of exploiting them as self‐assembling systems with interesting (opto)electronic properties; and charged systems, which are important for applications ranging from ionic liquids for green solvents to polyelectrolytes for exchange membranes and next‐generation energy storage devices.…”

“…Moreover, the Martini 3 parametrization has taken into account not only infinite dilution properties such as free energies of transfer but also miscibility data on binary mixtures. [ 292 ] As a consequence, the re‐calibrated Martini interaction matrix is expected to perform better in applications involving relative miscibility, self‐assembly, and aggregation propensities. Additionally, molecular packing is more accurate, as demonstrated for example in a recent biomolecular study where Martini 3 small molecules were able to find and bind to protein pockets in a wide range of systems with very high accuracy.…”

“…The upcoming new version of Martini 3 includes more generic interaction modifiers, generally dubbed “ labels”. Besides the hydrogen‐bonding labels already present in Martini 2, which have been expanded and can now [ 292 ] be applied to all the new N‐ and P‐bead types, also electron polarizability labels, which mimic the electron‐donor or electron‐acceptor character of certain aromatic fragments, and self‐interaction labels, which more generically decrease/increase the self‐interaction of a certain bead type without changing its free energy of transfer, were introduced. [ 292 ] Such labels expand the capabilities of Martini by giving the user a wider selection of pre‐calibrated bead types.…”

Off-Lattice Monte-Carlo Approach for Studying Nucleation and Evaporation Phenomena at the Molecular Scale

“…under different conditions (e.g., external fields). By using the framework of this study, these systems can be modeled by using any force-field (e.g., all-atom [ 34 ] and coarse-grained [ 35 , 36 ] models) at the particular temperature that the forcefield was obtained. Hence, our approach provides new areas of application for popular force-fields in nucleation and evaporation phenomena without the need for changing their parameters, since the processes are controlled at the LV interface by the chemical potential.…”

Perspectives on High-Throughput Ligand/Protein Docking With Martini MD Simulations

“…Overall, some limiting factors hampered the use of Martini in small-molecule and protein design: (1) chemical specificity to reproduce the broad chemical space of drugs; (2) the thermodynamics of ligand-protein and protein-protein interactions are generally overestimated (Stark et al, 2013;Javanainen et al, 2017;Alessandri et al, 2019); and (3) introduction of conformational flexibility in proteins requires case-by-case optimization (Negami et al, 2020;Ahalawat and Mondal, 2021). A new version of the Martini force field, named Martini 3 (Souza et al, 2021), partly solves these issues: it can represent a broader variety of chemical compounds, and it features improved molecular packing and optimized molecular interactions (along with specific interactions mimicking H-bonding and electronic polarizability). Recently, Martini 3 was successfully applied to a range of protein-ligand system examples, from the wellcharacterized T4 lysozyme to members of the GPCR family and nuclear receptors to a variety of enzymes (Souza et al, 2020).…”