Biology subjects

Grunewald, F.

Publications and source records attributed to Grunewald, F..

5 recordsLinked to original sources

bioRxiv2026

Extending the MAD Toolbox: New Polymer Builder and Enhanced Martini Database

The MArtini Database (MAD) web server (https://mad.ens-lyon.fr/) has been updated with new tools, models, and capabilities to support a broader range of molecular systems for the Martini coarse-grained (CG) force field. The most notable addition is the MAD:Polymer Builder, enabling the automated construction of CG polymer models with varying architectures and complexities. The server now incorporates the latest developments in Martini 3, providing enhanced control within the MAD:Molecule Builder over the conversion of all-atom structures into CG representations, including the implementation of G[o]Martini 3 for protein complexes and water-protein interaction biases. The MAD:Polymer Builder and MAD:Molecule Builder are both adapted to work with intrinsically disordered proteins and domains. Substantial progress has been made in expanding the MAD:Database, making a growing library of Martini-ready compounds readily accessible across the entire MAD ecosystem. These advances position MAD as a comprehensive and evolving platform for the preparation of diverse systems in CG molecular simulations.

bioinformatics↗

bioRxiv2024

Hybrid lipid-block copolymer membranes enable stable reconstitution of a wide range of nanopores and robust sampling of serum

Biological nanopores are powerful tools for detecting biomolecules at the single-molecule level, making them appealing as sensors for biological samples. However, the lipid membranes in which nanopores reside can be unstable in the presence of biological fluids. Here, membranes formed with the amphiphilic polymers PMOXA-PDMS-PMOXA and PBD-PEO are tested as potential alternatives for nanopore sensing. We demonstrate that polymer membranes can possess increased stability towards applied potentials and high concentrations of human serum, but that the stable insertion of a wide range of biological nanopores is most often compromised. Alternatively, hybrid polymer-lipid membranes comprising a 1:1 w/w mixture of PBD11PEO8 and DPhPC showed high electrical and biochemical stability while creating a suitable environment for all tested nanopores. Analytes such as proteins, DNA and sugars were efficiently sampled, indicating that in hybrid membranes nanopores showed native-like properties. Molecular dynamics simulations revealed that lipids form [~]12 nm domains interspersed by a polymer matrix. Nanopores partitioned into these lipid nanodomains and sequestered lipids possibly offering the same binding strength as in a native bilayer. This work shows that single-molecule analysis with nanopores in [PBD11PEO8 + DPhPC] membranes is feasible and present stable recordings in the presence of human serum. These results pave the way towards novel nanopore-based biosensors.

biophysics↗

bioRxiv2024

GoMartini 3: From large conformational changes in proteins to environmental bias corrections

Coarse-grained modeling has become an important tool to supplement experimental measurements, allowing access to spatio-temporal scales beyond all-atom based approaches. The G[o]Martini model combines structure- and physics-based coarse-grained approaches, balancing computational efficiency and accurate representation of protein dynamics with the capabilities of studying proteins in different biological environments. This paper introduces an enhanced G[o]Martini model, which combines a virtual-site implementation of G[o] models with Martini 3. The implementation has been extensively tested by the community since the release of the new version of Martini. This work demonstrates the capabilities of the model in diverse case studies, ranging from protein-membrane binding to protein-ligand interactions and AFM force profile calculations. The model is also versatile, as it can address recent inaccuracies reported in the Martini protein model. Lastly, the paper discusses the advantages, limitations, and future perspectives of the Martini 3 protein model and its combination with G[o] models.

biophysics↗

bioRxiv2023

Curvature-induced lipid sorting beyond the critical packing parameter

Over the last few decades, the spatial organization of biomembranes has received a lot of attention. With the fluid mosaic model, Singer and Nicolson proposed that biomembranes behave as two-dimensional fluids, allowing proteins and lipids to diffuse freely and thus react to external stimuli. Biological functionality and membrane organization are intricately linked to each other, however, how these organizations emerge is yet to be established. Here we use coarse-grained molecular dynamics simulations to explore the relationship between membrane shape and lateral organization at the nanoscale for a broad range of lipid mixtures. Our results illustrate that membrane curvature and lateral organization are intimately linked at the nanoscale and the relationship is much more complicated compared to the traditional views, in particular the lipid shape concept. Furthermore, we show that large membrane curvature can disrupt phase separation, line tension, and interleaflet coupling leading to non-intuitive lipid sorting. Our findings highlight how curvature-driven sorting can alter the phase behavior of lipid mixtures, which could be crucial for cellular functionality.

biophysics↗

bioRxiv2021

Molecular architecture of SARS-CoV-2 envelope by integrative modeling

Despite tremendous efforts by the research community during the COVID-19 pandemic, the exact structure of SARS-CoV-2 and related betacoronaviruses remains elusive. Being a key structural component of the SARS-CoV-2 virion, the envelope encapsulates viral RNA and is composed of three structural proteins, spike (S), membrane (M), and envelope (E), which interact with each other and with the lipids acquired from the host membranes. Here, we developed and applied an integrative multiscale computational approach to model the envelope structure of SARS-CoV-2 with near atomistic detail, focusing on studying the dynamic nature and molecular interactions of its most abundant, but largely understudied, M protein. The molecular dynamics simulations allowed us to test the envelope stability under different configurations and revealed that the M dimers agglomerated into large, filament-like, macromolecular assemblies with distinct molecular patterns formed by Ms transmembrane and intravirion (endo) domains. These results are in good agreement with current experimental data, demonstrating a generic and versatile integrative approach to model the structure of a virus de novo. We anticipate our work to provide insights into critical roles of structural proteins in the viral assembly and integration, proposing new targets for the antiviral therapies.

biophysics↗