Molecular Dynamics Simulation Suggests Possible Interaction Patterns at Early Steps of β2-Microglobulin Aggregation
| Autor: | Federico Fogolari, Alessandra Corazza, Vittorio Bellotti, Pietro Faccioli, Gennaro Esposito, Lidia Pieri, Pierfrancesco Zuccato, Paolo Viglino |
|---|---|
| Přispěvatelé: | Fogolari, F, Corazza, A, Viglino, P, Zuccato, P, Pieri, L, Faccioli, P, Bellotti, V, Esposito, G |
| Rok vydání: | 2007 |
| Předmět: |
Models
Molecular Work (thermodynamics) Protein Conformation Beta-2 microglobulin Chemistry Intermolecular force Biophysics Proteins Protein interactions Molecular dynamics Fibril formation Protein structure Computational chemistry Chemical physics Parallel arrangement Molecule Computer Simulation beta 2-Microglobulin Protein Binding |
| Zdroj: | Biophysical Journal. 92:1673-1681 |
| ISSN: | 0006-3495 |
| DOI: | 10.1529/biophysj.106.098483 |
| Popis: | Early events in aggregation of proteins are not easily accessible by experiments. In this work, we perform a 5-ns molecular dynamics simulation of an ensemble of 27 copies of beta(2)-microglobulin in explicit solvent. During the simulation, the formation of intermolecular contacts is observed. The simulation highlights the importance of apical residues and, in particular, of those at the N-terminus end of the molecule. The most frequently found pattern of interaction involves a head-to-head contact arrangement of molecules. Hydrophobic contacts appear to be important for the establishment of long-lived (on the simulation timescale) contacts. Although early events on the pathway to aggregation and fibril formation are not directly related to the end-state of the process, which is reached on a much longer timescale, simulation results are consistent with experimental data and in general with a parallel arrangement of intermolecular beta-strand pairs. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|