کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
444428 | 692981 | 2011 | 7 صفحه PDF | دانلود رایگان |
To investigate the molecular mechanisms involved in the very initial stages of protein unfolding, we carried out one long (1 μs) 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.
Figure optionsDownload high-quality image (199 K)Download as PowerPoint slideHighlights
► Long molecular dynamics reproduce early steps of the unfolding of an 18 kDa protein.
► Interactions of key residues are effective in monitoring early steps of unfolding.
► Urea is effective in dissolving the core hydrophobic region.
► Analysis of H-bonds suggests that urea affects the stability of their network.
Journal: Journal of Molecular Graphics and Modelling - Volume 30, September 2011, Pages 24–30