Identification And Optimization Of Lead Candidates
Muse® is a molecular design workflow designed to accelerate the identification and optimization of lead candidates. Using Muse, CADD Scientists and Medicinal Chemists identify novel structures, scaffolds, or side-chains that meet specific design objectives. With Muse, scientists can:
Muse uses ligand-based scoring to generate ideas that optimize the shape and pharmacophoric similarity to a set of lead structures, and comes with TupletScore, a robust scoring function, so users can immediately begin invention experiments.
TupletScore uses flexible templates and is valuable in situations where the conformation of the lead or active structures is unknown and also when the binding modes for the lead compounds is unknown. TupletScore takes into account Pharmacophore and Unity Tanimoto fingerprint similarity.
New Scoring Function for Multi-Parameter Optimization
TriposScore is an optional scoring function that can be used with Muse for ligand based multi-critera drug design. Developed in collaboration with AstraZeneca, TriposScore has been extensively validated in drug discovery projects. TriposScore uses a rigid 3D template and takes into account shape and pharmacophore similarity but also includes many more design criteria (E.g. cLogP, MW, TPSA, Lupinski Counts, Rotatable Bond Counts, ect…).
Like TupletScore, TriposScore allows users to add their own in-house 3rd party properties to the workflow.
Muse and TriposScore can be easily integrated with ANY scoring function, allowing the user to tailor experiments based on additional information he already has (E.g. Surflex-Dock, Topomer CoMFA or Topomer Search from Tripos, or computational chemistry programs from 3rd party vendors).
Designing Drugs Against Multiple Parameters -
Scoring functions for multi-parameter ligand based de novo design
James Damewood, Ph.D.; Principal Scientist II, AstraZeneca