Self-Assembly of Polymer-Encased Lipid Nanodiscs and Membrane Protein Reconstitution
| Autor: | Ayyalusamy Ramamoorthy, Takuya Genjo, Bikash R. Sahoo, Kanhu C. Moharana |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Chemical structure
Lipid Bilayers Molecular Dynamics Simulation 010402 general chemistry 01 natural sciences Article Amyloid beta-Protein Precursor Molecular dynamics Polymethacrylic Acids Rhodopsins Microbial 0103 physical sciences Copolymer Materials Chemistry Humans Amino Acid Sequence Physical and Theoretical Chemistry Nostoc Nanodisc chemistry.chemical_classification 010304 chemical physics Chemistry Integrin beta3 Maleates Polymer Transmembrane protein 0104 chemical sciences Surfaces Coatings and Films Membrane Membrane protein Phosphatidylcholines Biophysics Nanoparticles Polystyrenes Self-assembly Dimyristoylphosphatidylcholine |
| Zdroj: | J Phys Chem B |
| ISSN: | 1520-5207 1520-6106 |
| DOI: | 10.1021/acs.jpcb.9b03681 |
| Popis: | The absence of detergent and curvature makes nanodiscs to be excellent membrane mimetics. The lack of structural and mechanistic model of polymer-encapsulated lipid-nanodiscs limits their use to study the structure, dynamics and function of membrane proteins. In this study, we parametrized and optimized the coarse-graining (CG) bead-mapping for two differently charged and functionalized copolymers, namely styrene-maleic acid (SMAEA) and polymethacrylate (PMAQA), for the Martini force-field framework and showed nanodisc formation (< 8 nm diameter) on a time scale of tens of microseconds using molecular dynamics (MD) simulation. Structural models of ~ 2.0 or 4.8 kDa PMAQA and ~2.2 kDa SMAEA polymer based lipid-nanodiscs highlights the importance of polymer chemical structure, size and polymer:lipid molar ratio in the optimization of nanodisc structure. The ideal spatial arrangement of polymers in nanodisc, nanodisc size and thermal stability obtained from our MD simulation correlates well with the experimental observations. The polymer-nanodisc were tested for the reconstitution of single-pass or multi-pass transmembrane proteins. We expect this study to be useful in the development of novel polymer based lipid-nanodiscs and for the structural studies of membrane proteins.TOC GRAPHICS |
| Databáze: | OpenAIRE |
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