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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, for example, hydrogen bonding and electronic polarizability. The updated 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.

As molecular dynamics simulations increase in complexity, new analysis tools are necessary to facilitate interpreting the results. Lipids, for instance, are known to form many complicated morphologies, because of their amphipathic nature, becoming more intricate as the particle count increases. A few lipids might form a micelle, where aggregation of tens of thousands could lead to vesicle formation. Millions of lipids comprise a cell and its organelle membranes, and are involved in processes such as neurotransmission and transfection. To study such phenomena, it is useful to have analysis tools that understand what is meant by emerging entities such as micelles and vesicles. Studying such systems at the particle level only becomes extremely tedious, counterintuitive, and computationally expensive. To address this issue, we developed a method to track all the individual lipid leaflets, allowing for easy and quick detection of topological changes at the mesoscale. By using a voxel-based approach and focusing on locality, we forego costly geometrical operations without losing important details and chronologically identify the lipid segments using the Jaccard index. Thus, we achieve a consistent sequential segmentation on a wide variety of (lipid) systems, including monolayers, bilayers, vesicles, inverted hexagonal phases, up to the membranes of a full mitochondrion. It also discriminates between adhesion and fusion of leaflets. We show that our method produces consistent results without the need for prefitting parameters, and segmentation of millions of particles can be achieved on a desktop machine.

The use of non-viral vectors for in vivo gene therapy could drastically increase safety, whilst reducing the cost of preparing the vectors. A promising approach to non-viral vectors makes use of DNA/cationic liposome complexes (lipoplexes) to deliver the genetic material. Here we use coarse-grained molecular dynamics simulations to investigate the molecular mechanism underlying efficient DNA transfer from lipoplexes. Our computational fusion experiments of lipoplexes with endosomal membrane models show two distinct modes of transfection: parallel and perpendicular. In the parallel fusion pathway, DNA aligns with the membrane surface, showing very quick release of genetic material shortly after the initial fusion pore is formed. The perpendicular pathway also leads to transfection, but release is slower. We further show that the composition and size of the lipoplex, as well as the lipid composition of the endosomal membrane, have a significant impact on fusion efficiency in our models.