- 本系公告 /
Coarse-Grained Molecular Dynamics of Biomolecular Self-Assembly: Membranes, Vesicles, and Lipid Nanoparticles
Professor Wataru Shinoda
We illustrate our coarse-grained (CG) molecular modeling of biomolecular self-assemblies. Our CG model, initially called the Shinoda-DeVane-Klein (SDK) model but now renamed the SPICA force field, reproduces reasonable interfacial and thermodynamic properties of lipid assembly, including experimental values for surface/interfacial tension, density, solvation/transfer free energies, and simultaneously reproduces structural data such as molecular distributions obtained from all-atom MD simulations. The SPICA FF also allows the prediction of realistic elastic moduli and line tensions of lipid membranes, thus ensuring quantitative prediction of lipid aggregate morphology. CG modeling of cholesterol and sphingomyelin (SM) successfully discussed phase separation or domain formation within lipid membranes. Liquid ordered domains in two opposing leaflets are registered and anti-registered depending on the lipid species, suggesting the importance of hydrophobic mismatch and interdigitation. Inter-leaflet coupling is examined using long SM(LSM). We detected a striking effect of LSM on the phase state of the opposing leaflet. We also would like to demonstrate the extension of the SPICA FF for proteins and DNA/RNA. We show the CG model works well for HBV virus capsid systems and lipid nanoparticles (LNPs), the latter is a great candidate of the nano-carrier for gene delivery. MD simulation with the SPICA FF can handle the molecular system of over 100 nm, which is large enough to accommodate ordinary LNPs. Time permitting, we would like to present the recent results of CG-MD simulations for endosomal escape of LNPs.
1998-2000 Mitsubishi Chemical Co.
2000-2001 National Institute of Materials and Chemistry
2001-2013 National Institute of Advanced Industrial Science and Technology
(2005-2007 University of Pennsylvania, Visiting Scholar)
2014-2021 Nagoya University, Grad School of Engineering, Associate Professor
2021- Okayama University, Research Institute for Interdisciplinary Science, Professor