bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2022, Volume and Issue: unknown
Published: Nov. 10, 2022
Peripheral proteins, known to induce curvature, have been identified as key agents in the spontaneous remodeling of bilayer membranes, leading invaginations and genesis membrane tubules. For proteins like cholera Shiga toxin, which impart with locally isotropic curvatures, resultant membrane-mediated interactions remain notably subtle. Consequently, collective action these culminating formation dense clusters on subsequent invagination, unfolds over an extended timescale, often spanning several minutes. This gradual progression challenges direct simulation invagination process, even coarsegrained models. In this study, we introduce a steered molecular dynamics protocol wherein peripheral are impelled converge patch, instigating invagination. Utilizing Jarzynski equality, derive free energy profile process from suite non-equilibrium replicas. Examining two distinct membrane-associated elucidate influence protein flexibility distribution induced curvatures both corresponding profile. We delve into role effects shaping organization within invaginated domain. Building profile, model Markovian offer estimates timescales. Our findings yield minute-long implied timescales that resonate well empirical observations.
Language: Английский