Discovery of High-Affinity Amyloid Ligands Using a Ligand-Based Virtual Screening Pipeline.

ABSTRACT: Fibrillar protein aggregates are characteristic of neurodegenerative diseases but represent difficult targets for ligand design, because limited structural information about the binding sites is available. Ligand-based virtual screening has been used to develop a computational method for the selection of new ligands for Aβ(1-42) fibrils, and five new ligands have been experimentally confirmed as nanomolar affinity binders. A database of ligands for Aβ(1-42) fibrils was assembled from the literature and used to train models for the prediction of dissociation constants based on chemical structure. The virtual screening pipeline consists of three steps: a molecular property filter based on charge, molecular weight, and logP; a machine learning model based on simple chemical descriptors

SUBMITTER: Chisholm TS 

PROVIDER: S-EPMC10375536 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature