Fast Parametrization of Martini3 Models for Fragments and Small Molecules

Coarse-grained molecular dynamics simulations, such as those performed with the recently parametrized Martini 3 force field, simplify molecular models and enable the study of larger systems over longer time scales. With this new implementation, Martini 3 allows more bead types and sizes, becoming more amenable to studying dynamical phenomena involving small molecules such as protein–ligand interactions and membrane permeation. However, while solutions existed to automatically model small molecules using the previous iteration of the Martini force field, there is no simple way to generate such molecules for Martini 3 yet. Here, we introduce Auto-MartiniM3, an advanced and updated version of the Auto-Martini program designed to automate the coarse-graining of small molecules to be used with the Martini 3 force field. We validated our approach by modeling 81 simple molecules from the Martini Database and comparing their structural and thermodynamic properties with those obtained from models designed by Martini experts. Additionally, we assessed the behavior of Auto-MartiniM3-generated models by calculating solute translocation and free energy across lipid bilayers. We also evaluated more complex molecules such as caffeine by testing its binding to the adenosine A2A receptor. Finally, our results from deploying Auto-MartiniM3 on a large data set of molecular fragments demonstrate that this program can become a tool of choice for fast, high-throughput creation of coarse-grained models of small molecules, offering a good balance between automation and accuracy. Auto-MartiniM3 source code is freely available at https://github.com/Martini-Force-Field-Initiative/Automartini_M3.

pubs.acs.org

The Martini 3 Lipidome: Expanded and Refined Parameters Improve Lipid Phase Behavior

Lipid membranes are central to cellular life. Complementing experiments, computational modeling has been essential in unraveling complex lipid-biomolecule interactions, crucial in both academia and industry. The Martini model, a coarse-grained force field for efficient molecular dynamics simulations, is widely used to study membrane phenomena but has faced limitations, particularly in capturing realistic lipid phase behavior. Here, we present refined Martini 3 lipid models with a mapping scheme that distinguishes lipid tails that differ by just two carbon atoms, enhancing the structural resolution and thermodynamic accuracy of model membrane systems including ternary mixtures. The expanded Martini lipid library includes thousands of models, enabling simulations of complex and biologically relevant systems. These advancements establish Martini as a robust platform for lipid-based simulations across diverse fields.

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GōMartini 3: From large conformational changes in proteins to environmental bias corrections - Nature Communications

This work presents GōMartini 3, an improved coarse-grained protein model combining physics- and structure-based approaches. It boosts computational efficiency and accuracy for structured soluble and m...

nature.com

doi.org

Computational Methods for Modeling Lipid-Mediated Active Pharmaceutical Ingredient Delivery

Lipid-mediated delivery of active pharmaceutical ingredients (API) opened new possibilities in advanced therapies. By encapsulating an API into a lipid nanocarrier (LNC), one can safely deliver APIs n...

doi.org

Systematic Approach to Parametrization of Disaccharides for the Martini 3 Coarse-Grained Force Field

Sugars are ubiquitous in biology; they occur in all kingdoms of life. Despite their prevalence, they have often been somewhat neglected in studies of structure–dynamics–function relationships of macro...

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Martini 3 coarse-grained models for carbon nanomaterials

The Martini model is a coarse-grained force field allowing simulations of biomolecular systems as well as a range of materials, including different types of nanomaterials of technological interest. Re...

chemrxiv.org