ZINC-22─A Free Multi-Billion-Scale Database of Tangible Compounds for Ligand Discovery

Area of Science:

• Computational Chemistry
• Drug Discovery
• Cheminformatics

Background:

• Purchasable chemical space has expanded dramatically, presenting challenges for existing ligand discovery tools.
• The scale of available molecules strains current methods for searching and analyzing chemical libraries.

Purpose of the Study:

• To introduce ZINC-22, a database of commercially accessible small molecules from large-scale make-on-demand libraries.
• To develop efficient tools for navigating and analyzing this expanded chemical space for drug discovery.
• To assess the impact of database growth on molecular diversity.

Main Methods:

• Development of the ZINC-22 database and the CartBlanche graphical user interface (GUI).
• Implementation of sublinear-scaling similarity search methods for efficient analog searching.
• Utilizing advanced data organization for rapid retrieval of molecular properties (conformations, partial atomic charges, cLogP, solvation energies).

Main Results:

• ZINC-22 provides access to billions of make-on-demand molecules.
• CartBlanche enables facile analog searching and rapid property lookup, overcoming previous performance bottlenecks.
• Molecular diversity, measured by Bemis-Murcko scaffolds, continues to increase with database size, particularly for larger molecules.

Conclusions:

• ZINC-22 and its associated tools effectively manage and exploit vast chemical libraries for ligand discovery.
• The database demonstrates sustained molecular diversity, crucial for exploring novel chemical matter.
• The findings have implications for the future development of chemical databases approaching trillion-molecule scales.