title: Molecular dynamics simulation suggests possible interaction patterns at early steps of beta2-microglobulin aggregation.
abstract: 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.
authors.affiliation: Dipartimento di Scienze e Tecnologie Biomediche, Università di Udine, Udine, Italy. ffogolari@mail.dstb.uniud.it
authors.forename: Federico
authors.initials: F
authors.lastname: Fogolari
authors.forename: Alessandra
authors.initials: A
authors.lastname: Corazza
authors.forename: Paolo
authors.initials: P
authors.lastname: Viglino
authors.forename: Pierfrancesco
authors.initials: P
authors.lastname: Zuccato
authors.forename: Lidia
authors.initials: L
authors.lastname: Pieri
authors.forename: Pietro
authors.initials: P
authors.lastname: Faccioli
authors.forename: Vittorio
authors.initials: V
authors.lastname: Bellotti
authors.forename: Gennaro
authors.initials: G
authors.lastname: Esposito
mesh_terms: D003198:Computer Simulation; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D001613:beta 2-Microglobulin / Q000737:chemistry* / Q000378:metabolism
chemical_list: D001613:beta 2-Microglobulin