What factor drives the fibrillogenic association of beta-sheets?
The identification of the driving factor for fibril formation is paramount to understand the molecular basis of amyloidogenic disease. Recently, an atomic-detail structure of a fibrillogenic aggregate was reported and revealed a tight packing of beta-sheets. However, there is not a single pair-wise interaction of significance between the beta-sheets, no hydrogen bond and no hydrophobic interaction. Instead, there is extensive burial of polar groups at the interface. These observations lead to the question: What factor drives the association of beta-sheets? This issue is addressed by combining all-atom molecular dynamics with an implicit-solvent analysis. The driving force for the association arises from the mechanical equivalent of the dehydration propensity of pre-formed intra-sheet hydrogen bonds and dipole-dipole interactions.
Fernández
Ariel
A
Department of Bioengineering, Rice University, Houston, TX 77005, United States. arifer@rice.edu
D000682:Amyloid / Q000737:chemistry*; D006801:Humans; D006860:Hydrogen Bonding; D008958:Models, Molecular; D017433:Protein Structure, Secondary; D012997:Solvents; D013816:Thermodynamics; D014867:Water
D000682:Amyloid; D012997:Solvents; D014867:Water