RT Journal Article
SR Electronic
T1 Hydrogen Bond Networks and Hydrophobic Effects in the Amyloid β30–35 Chain in Water: A Molecular Dynamics Study
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 090092
DO 10.1101/090092
A1 KwangHyok Jong
A1 Luca Grisanti
A1 Ali Hassanali
YR 2016
UL http://biorxiv.org/content/early/2016/11/28/090092.abstract
AB We study the conformational landscape of the C-terminal fragment of the Amyloid protein Aβ30–35 in water using well-tempered metadynamics simulations and find that it resembles an intrinsically disordered protein. The conformational fluctuations of the protein are facilitated by a collective reorganization of both protein and water hydrogen bond networks, combined with electrostatic interactions between termini as well as hydrophobic interactions of the side chains. The stabilization of hydrophobic interactions in one of the conformers involves a collective collapse of the sidechains along with a squeeze out of water sandwiched in between. The charged N and C termini play a critical role in stabilizing different types of protein conformations including those involving contact ion salt-bridges as well as solvent mediated interactions of the termini and amide backbone. We examine this by probing the distribution of directed water wires forming the hydrogen bond network enveloping the polypeptide. Water wires and their fluctuations form an integral part of structural signature of the protein conformation.