Assembly and dynamics of viral membrane proteins in lipid bilayers - a molecular dynamics simulation study
| Autor: | Meng-Han Lin, 林孟翰 |
|---|---|
| Rok vydání: | 2015 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 104 Computational methods such as molecular dynamics (MD) simulations are used to address biological questions which are related to the assembly and dynamics of viral membrane proteins: how do membrane proteins such as viral non-structural protein 4 A (NS4A) induce membrane curvature, and how does Vpu of human immunodeficiency virus type-1 (HIV-1) oligomerize within the lipid membrane. Dengue virus NS4A is an integral membrane protein which is located in endoplasmic reticulum (ER) and can turn the membrane into vesicle like features, the so called replication vesicles. Within these vesicle-like structures, RNA replication is facilitated. Structural details of NS4A are not known. The protein and the membrane system is created at atomic level. The simulations show that a single NS4A can cause membrane curvature. Previous studies show that the transmembrane domain (TMD) of Vpu could be a tetramer, pentamer or hexamer. Using coarse graining MD (CGMD) simulation, Vpu assembles with three binding sites into a series of oligomers. Not only the TMDs but also cytoplasmic domains are involved in the dynamics of self-assembly. Negative charges, as in the case of the two phosphorylated sites in the cytoplasmic domain of Vpu, extend the time for assembly and prevent the formation of larger clusters because of the repulsion of negative charged phosphatess. Protein-protein interaction (PPI) of globular proteins is studied as comparison. A protein docking tool is used to predict a potential assembly of the epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF) complex. In docked structures the binding site of VEGF to its receptor VEGFR was partially occluded by EGF. The binding site of EGF for its receptor EGFR was unaffected. With steered MD simulation in combination with the umbrella sampling (US) binding free energy of the proposed binding pose is proposed on the basis of potentials of mean force calculations. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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