Martini 3 Coarse-Grained Force Field for Carbohydrates.

The Martini 3 force field is a full reparametrization of the Martini coarse-grained model for biomolecular simulations. Due to the improved interaction balance, it allows for a more accurate description of condensed phase systems. In the present work, we develop a consistent strategy to parametrize carbohydrate molecules accurately within the framework of Martini 3. In particular, we develop a canonical mapping scheme which decomposes arbitrarily large carbohydrates into a limited number of fragments. Bead types for these fragments have been assigned by matching physicochemical properties of mono- and disaccharides. In addition, guidelines for assigning bonds, angles, and dihedrals were developed. These guidelines enable a more accurate description of carbohydrate conformations than in the Martini 2 force field. We show that models obtained with this approach are able to accurately reproduce osmotic pressures of carbohydrate water solutions. Furthermore, we provide evidence that the model differentiates correctly the solubility of the polyglucoses dextran (water-soluble) and cellulose (water insoluble but soluble in ionic liquids). Finally, we demonstrate that the new building blocks can be applied to glycolipids. We show they are able to reproduce membrane properties and induce binding of peripheral membrane proteins. These test cases demonstrate the validity and transferability of our approach.

Computational Virology: Molecular Simulations of Virus Dynamics and Interactions.

Molecular modelling and simulations play a key role in computational virology, allowing us to study viruses and their components. This allows experimental structures and related information to be integrated into a single coherent model, enabling predictions about the behaviour of a viral system to go beyond what could be obtained experimentally. In this way, computational approaches provide a powerful complement to more traditional experimental and structural methods. In this chapter, we describe three main areas of computational virology to showcase the power of methods within this field. We begin by describing relatively small simulation systems and focusing on the behaviour of fusion peptides. Then, extending to longer timescales and larger systems, we discuss computational studies of viral capsid assembly and genome encapsidation. Finally, we describe recent developments which allow entire viral particles to be simulated.

Multiscale simulations reveal conserved patterns of lipid interactions with aquaporins.

Interactions of membrane proteins with lipid molecules are central to their stability and function. We have used multiscale molecular dynamics simulations to determine the extent to which interactions with lipids are conserved across the aquaporin (Aqp) family of membrane proteins. Simulation-based assessment of the lipid interactions made by Aqps when embedded within a simple phospholipid bilayer agrees well with the protein-lipid contacts determined by electron diffraction from 2D crystals. Extending this simulation-based analysis to all Aqps of known structure reveals a degree of conservation of such interactions across the Aqp structural proteome. Despite similarities in the binding orientations and interactions of the lipids, there do not appear to be distinct, high-specificity lipid binding sites on the surface of Aqps. Rather Aqps exhibit a more broadly conserved protein/lipid interface, suggestive of interchange between annular and bulk lipids, instead of a fixed annular "shell" of lipids.