Coarse-grained molecular dynamics simulations of bio- and macromolecular systems offer a method of accessing otherwise unobtainable time and length scales, compared to atomistic simulation techniques. However, a limiting step is often the generation and validation of the coarse-grained models. Here, we describe a new software package, Fast-Forward, which aids parametrization of models for the widely used Martini coarse-grained force field. In comparison to other similar packages, Fast-Forward offers a system-agnostic suite of tools to parametrize molecules of any size, existing in any environment. It achieves this while maintaining ease of use and the use of interoperable file formats from the Martini software ecosystem. Through its three subprograms, the package offers tools for trajectory mapping, parameter generation, and model validation. We demonstrate the potential of the package for several different use cases, from small biological molecules (glutathione and glutathione disulfide) to models of synthetic polymers (poly(methyl methacrylate), PMMA).
Christopher Brasnett, Maximilian Fidlin, Thilo Duve et al.· Journal of Chemical Informat...· 0 citations
Mitochondrial cristae are essential for respiration, yet the molecular basis of how the high curvature of these membrane folds is maintained remains unclear. Using structure prediction tools and multiscale simulations, we examined the role of the MIC10 subcomplex of the mitochondrial contact site and cristae organizing system (MICOS). We found that the MIC10 proteins Mic10, Mic26, and Mic27 strongly recruit cardiolipin at conserved positive loop motifs, driving oligomerization of these subunits and resulting in the stabilization of curvature in model membranes. Reconstruction of the full MIC10 complex in a realistic crista junction setup shows its capability to maintain membrane bending, while intrinsically disordered regions may form a permeability barrier between cristae and the intermembrane space. These findings provide a mechanistic model for cristae curvature formation and suggest how MICOS components cooperate with cardiolipins to maintain mitochondrial architecture.
Chelsea M. Brown, T. Wassenaar, Z. Freyberg et al.· Science Advances· 0 citations