Biology subjects

Monticelli, L.

Publications and source records attributed to Monticelli, L..

3 recordsLinked to original sources

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

Birth of an organelle: molecular mechanism of lipid droplet biogenesis

Lipid droplets (LDs) are cellular organelles regulating energy and lipid metabolism. Generated in the endoplasmic reticulum (ER) by phase separation of neutral lipids (e.g., triglycerides), nascent LDs resemble lens-shaped blisters, grow into spherical droplets, and eventually emerge from the ER membrane, generally towards the cytosol - a process known as budding. Images of both nascent and mature LDs are available, but the mechanism of biogenesis has never been observed experimentally. Here we identify the mechanism of the initial steps in LD biogenesis using computer simulations at the molecular level, emulating LD growth in ER-mimicking membranes. We find that LDs bud towards the cytosol only when sufficient asymmetry is generated between the two membrane leaflets: the budding transition is independent of membrane morphology, lipid composition, and LD size. Seipin, a protein essential for correct LD biogenesis, is per se not sufficient to promote budding, but it stabilizes LD-ER contact sites. Localization of triglyceride synthesis in the proximity of seipin is necessary to avoid nucleation of multiple LDs - a possible cause of aberrant phenotypes. In contrast, localization of phospholipid synthesis has no effect on the mechanism of budding. Our new methodology paves the way to simulations of organelle and cell biogenesis.

biophysics↗

bioRxiv2022

Coarse-graining made easy with the MArtini Database Server

The MArtini Database (MAD - www.mad.ibcp.fr) is a web server designed for the sharing structures and topologies of molecules parameterized with the Martini coarse-grained (CG) force field. MAD can also convert atomistic structures into CG structures and prepare complex systems (including proteins, lipids etc.) for molecular dynamics (MD) simulations at the CG level. It is dedicated to the generation of input files for Martini 3, the most recent version of this popular CG force field. Specifically, the MAD server currently includes tools to submit or retrieve CG models of a wide range of molecules (lipids, carbohydrates, nanoparticles, etc.), transform atomistic protein structures into CG structures and topologies, with fine control on the process and assemble biomolecules into large systems and deliver all files necessary to start simulations in the GROMACS MD engine.

biophysics↗