This project involves a new computational methodology developed to address a fundamental challenge in the computer simulation of complex biomolecular systems: the interfacing and feedback between multiple spatial and temporal scales. Biomolecular systems can possess dynamics that occur on time scales ranging from the microscopic (nanoseconds) to the macroscopic (milliseconds to hours), and on length scales from Angstroms to millimeters and beyond. The specific goal of the project will be to simulate such processes in lipid bilayers (cell membranes). The focus will therefore be on the development and application of the new simulation technology to explore the nonlinear response of biomembranes to external perturbations such as mechanical stresses, pH gradients, osmotic forces, etc. The research will utilize an integrated computer simulation capability to link the microscopic, atomic level simulation information with macro-scale, continuum-level modeling. Viewed in its broadest context, this interdisciplinary project represents a step toward the eventual simulation of the key components of living organisms beginning with atomistic simulation information at its foundation. In the shorter term, the capability to model the response of a cell membrane to various environmental perturbations opens a pathway to design agents to modulate the properties of cell membranes in other contexts; for example, to increase/decrease susceptibility to lysis, to modulate permeability of specific bilayers in order to increase drug transport and to help design novel liposomes for drug delivery purposes.
| Madsen, Jesper J; Grime, John M A; Rossman, Jeremy S et al. (2018) Entropic forces drive clustering and spatial localization of influenza A M2 during viral budding. Proc Natl Acad Sci U S A 115:E8595-E8603 |
| Simunovic, Mijo; Bassereau, Patricia; Voth, Gregory A (2018) Organizing membrane-curving proteins: the emerging dynamical picture. Curr Opin Struct Biol 51:99-105 |
| Simunovic, Mijo; Manneville, Jean-Baptiste; Renard, Henri-François et al. (2017) Friction Mediates Scission of Tubular Membranes Scaffolded by BAR Proteins. Cell 170:172-184.e11 |
| Simunovic, Mijo; Šari?, An?ela; Henderson, J Michael et al. (2017) Long-Range Organization of Membrane-Curving Proteins. ACS Cent Sci 3:1246-1253 |
| Davtyan, Aram; Simunovic, Mijo; Voth, Gregory A (2017) The mesoscopic membrane with proteins (MesM-P) model. J Chem Phys 147:044101 |
| Simunovic, Mijo; Evergren, Emma; Golushko, Ivan et al. (2016) How curvature-generating proteins build scaffolds on membrane nanotubes. Proc Natl Acad Sci U S A 113:11226-11231 |
| Davtyan, Aram; Simunovic, Mijo; Voth, Gregory A (2016) Multiscale simulations of protein-facilitated membrane remodeling. J Struct Biol 196:57-63 |
| Simunovic, Mijo; Voth, Gregory A (2015) Membrane tension controls the assembly of curvature-generating proteins. Nat Commun 6:7219 |
| Simunovic, Mijo; Voth, Gregory A; Callan-Jones, Andrew et al. (2015) When Physics Takes Over: BAR Proteins and Membrane Curvature. Trends Cell Biol 25:780-792 |
| Li, Jianing; Ziemba, Brian P; Falke, Joseph J et al. (2014) Interactions of protein kinase C-? C1A and C1B domains with membranes: a combined computational and experimental study. J Am Chem Soc 136:11757-66 |
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