Covalent serine binders library is a comprehensive collection of compounds specifically designed to bind to serine targets. This library consists of 10 warhead scaffolds and a total of 4,400 compounds.
The preparation algorithm involves several steps to ensure the quality and diversity of the library. Firstly, a set of SMARTS queries, which capture selective warheads for serine binding based on literature extraction, are prepared. These SMARTS patterns serve as a guide to identify potential structures in the chemical inventory.
To filter out undesired structural motifs, the entire compound inventory, which comprises 1.6 million compounds, undergoes the REOS filter. It eliminates structurally unfavorable compounds from consideration. The filtered inventory is then searched for structures that match the warhead SMARTS patterns, thereby identifying potential candidates for the library.
Within each warhead scaffold set, diversity picking is applied using the MaxMin algorithm. This process ensures that the selected compounds are structurally diverse, with an internal set similarity threshold of 0.4 (measured using the Tanimoto coefficient and ECFP4 fingerprints with 2048 bits). The most diverse structures are retained, while similar structures can be ordered separately to establish structure-activity relationships (SAR) for potential hits.
The resulting library consists of 4,468 compounds that are considered suitable for medicinal chemistry (MedChem) applications. These compounds do not include the most active REOS 2 structures. The library includes 10 warhead patterns, with representative molecules ranging from 3 to 3,000 in each pattern, providing a diverse and comprehensive collection of compounds.
It is worth noting that highly diverse structures within each warhead pattern are retained, further enhancing the library’s potential for serine binding. By utilizing this carefully designed library, researchers and scientists can explore various interactions with serine targets and potentially discover novel compounds with therapeutic value.
