Staphylococcus aureus Sortase A Inhibitors Library

Staphylococcus aureus Sortase A Inhibitors Library

The ChemDiv Staphylococcus aureus Sortase A Inhibitors library is positioned as a robust chemogenomic resource for anti-staphylococcal drug discovery. It targets Sortase A, a validated anti-virulence target featuring intrinsically disordered regions, by leveraging the dynamic nature of the target.

Library Properties

• The library contains a total of 22,127 compounds.
• It features over 20,000 focused compounds.
• It includes over 700 compounds with high predicted ligand efficiency (LE).
• The compounds within the library are MedChem compatible.

Compound Classification

The library is divided into four specific types:

Methodology and Preparation Algorithm

• The library is the first practical output of ensemble-based virtual screening that moves beyond single-structure dogma.
• The methodology integrates previous advances, including the generation of 100 conformations via molecular dynamics (MD), the development of ensemble docking for peptidomimetics using MD-derived conformational ensembles, and the incorporation of explicit MD simulations into large-scale virtual screening.
• The library's preparation algorithm begins with ChemDiv stock, applies PAINS filters and ML filtering clustering, performs ensemble molecular docking of cluster centroids using AD-GPU, and concludes with cluster expansion.

Rational Design and Benefits

• The library is rationally designed based on ensemble docking scores and conformational coverage.
• Each compound is prioritized for its favourable binding free energy profile across the dominant SrtA conformers.
• This approach statistically enriches hit rates in biochemical assays.
• The design minimises conformation-dependent false negatives.
• The collection provides a mechanistically sound starting point for experimental validation.