To investigate the molecular mechanisms involved in the very initial stages of protein unfolding, we carried out one long (1μs) simulation of bovine β-lactoglobulin (BLG) together with three (500 ns) supporting MD runs, in which the unfolding conditions were produced by adding the osmolyte urea to the simulated systems and/or by increasing the thermal energy raising the temperature from 300 to 350 K. BLG was chosen, since it is a well-characterized model protein, for which structural and folding properties have been widely investigated by X-ray and NMR. MD trajectories were analyzed not only in terms of standard progress variables, such as backbone H-bonds, gyration radius width, secondary structure elements, but also through the scrutiny of interactions and dynamical behavior of specific key residues previously pointed out and investigated by NMR and belonging to a well known hydrophobic cluster. MD trajectories simulated in different unfolding conditions suggest that urea destabilizes BLG structure weakening protein::protein hydrophobic interactions and the hydrogen bond network. The early unfolding events, better observed at higher temperature, affect both secondary and tertiary structure of the protein.
Simulation of urea-induced protein unfolding: a lesson from bovine beta-lactoglobulin / I. Eberini, A. Emerson, C. Sensi, L. Ragona, P. Ricchiuto, A. Pedretti, E. Gianazza, A. Tramontano. - In: JOURNAL OF MOLECULAR GRAPHICS & MODELLING. - ISSN 1093-3263. - 30(2011), pp. 24-30.
|Titolo:||Simulation of urea-induced protein unfolding: a lesson from bovine beta-lactoglobulin|
EBERINI, IVANO (Corresponding)
GIANAZZA, ELISABETTA (Penultimo)
|Parole Chiave:||Molecular dynamics; Nuclear magnetic resonance; Protein structure; Osmolyte|
|Settore Scientifico Disciplinare:||Settore BIO/10 - Biochimica|
|Data di pubblicazione:||2011|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/j.jmgm.2011.06.004|
|Appare nelle tipologie:||01 - Articolo su periodico|