Identification of small-molecule binding pockets in the soluble monomeric form of the Aβ42 peptide.

ABSTRACT: The aggregation of intrinsically disordered peptides and proteins is associated with a wide range of highly debilitating neurological and systemic disorders. In this work we explored the potential of a structure-based drug discovery procedure to target one such system, the soluble monomeric form of the Aβ42 peptide. We utilised for this purpose a set of structures of the Aβ42 peptide selected from clusters of conformations within an ensemble generated by molecular dynamics simulations. Using these structures we carried out fragment mapping calculations to identify binding "hot spots" on the monomeric form of the Aβ42 peptide. This procedure provided a set of hot spots with ligand efficiencies comparable to those observed for structured proteins, and clustered into binding pockets. Such bin

SUBMITTER: Zhu M 

PROVIDER: S-EPMC5011423 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature