Combinatorial Virtual Screening

Ignite™ is a technology that enables rapid 3D virtual screening of combinatorial chemical spaces. Conventional virtual screening of large data sets is typically carried out by comparing 2D molecular fingerprints. This makes screening relatively fast but has the drawback that top-scoring results are less likely to be actual hits. As molecules are three-dimensional in nature, screening molecules with 3D descriptors can lead to more reliable hit detection. The 3D descriptors in Ignite use Cresset field technology to describe molecule in terms of electrostatics and shape.

Synthesizable chemical spaces are vast and routinely contain billion of molecules, making the fully enumerated libraries practically impossible to search. Ignite leverages the combinatorial nature of most chemical spaces i.e., a relatively small number of building blocks/fragments are combined to create a much larger number of enumerated compounds.

The Ignite algorithm performs a fast initial screen in reagent space. Reagents for each virtual library are converted into ‘product-like’ fragments, converting their reacting functional groups into minimal representations of the library products. These product-like fragments are then screened against the query molecule to determine which ones are likely to provide significant shape and electrostatic similarity.

Only the highest-scoring fragments are passed through to the next stage, where they are combined with the synthons from the other half of the reagent space. The combined molecule is then overlayed with the query molecule and scored again.