Towards the design and computational characterization of a membrane protein
| Autor: | D.P Tieleman, David Cregut, H.J.C. Berendsen, C.T. Choma, L. Serrano |
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| Přispěvatelé: | Moleculaire Dynamica |
| Rok vydání: | 2002 |
| Předmět: |
Models
Molecular MOLECULAR-DYNAMICS SIMULATIONS INFLUENZA-A VIRUS Molecular dynamics ION CHANNELS STRUCTURAL CHARACTERIZATION LIPID BILAYERS Materials Chemistry de novo design Computer Simulation Physical and Theoretical Chemistry Lipid bilayer 4-STRANDED COILED COILS Spectroscopy Helix bundle coiled coil Chemistry Membrane Proteins Computer Graphics and Computer-Aided Design molecular dynamics Transmembrane protein Characterization (materials science) Protein Structure Tertiary Crystallography Core (game theory) 4-HELIX BUNDLE Bundle CAPPING BOX Simulated annealing simulated annealing DE-NOVO DESIGN Biological system Peptides TRANSMEMBRANE ALPHA-HELICES |
| Zdroj: | Journal of Molecular Graphics & Modelling, 20(3), 219-234 |
| ISSN: | 1093-3263 |
| Popis: | The design of a transmembrane four-helix bundle is described. We start with an idealized four-helix bundle geometry, then use statistical information to build a plausible transmembrane bundle. Appropriate residues are chosen using database knowledge on the sequences of membrane helices and loops, then the packing of the bundle core is optimized, and favorable side chain rotamers from rotamer libraries are selected. Next, we use explicit physical knowledge from biomolecular simulation force fields and molecular dynamics simulations to test whether the designed structure is physically possible. These procedures test whether the designed protein will indeed be α-helical, well packed and stable over a time scale of several nanoseconds in a realistic lipid bilayer environment. We then test a modeling approach that does not include sophisticated database knowledge about proteins, but rather relies on applying our knowledge of the physics that governs protein motions. This independent validation of the design is based on simulated annealing and restrained molecular dynamics simulation in vacuo, comparable to procedures used to refine NMR and X-ray structures. |
| Databáze: | OpenAIRE |
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