PT - JOURNAL ARTICLE AU - KwangHyok Jong AU - Luca Grisanti AU - Ali Hassanali TI - Hydrogen Bond Networks and Hydrophobic Effects in the Amyloid <em>β</em><sub>30–35</sub> Chain in Water: A Molecular Dynamics Study AID - 10.1101/090092 DP - 2016 Jan 01 TA - bioRxiv PG - 090092 4099 - http://biorxiv.org/content/early/2016/11/28/090092.short 4100 - http://biorxiv.org/content/early/2016/11/28/090092.full 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.