Peptide to Non-Peptide: a Revolution in Virtual Screening

Peptide inhibitors of proteases and receptors are well known and relatively easy to find. However, poor ADMET properties limit their widespread use. To mimic a peptide with a small orally bioavailable drug remains the goal of most medicinal chemistry programs. A new description of inhibitors of biological targets will be presented. The surface and shape properties of a molecule are described as 'field points'. These descriptors can be encoded as a 1D vector, which when combined with a similarity metric allows molecules' field properties to be rapidly compared. Population of a database with commercially available compounds and comparison of a known active to the database allows virtual screening using fields to be applied to lead discovery.

Validation on a GPCR target returned a 30% hit rate (activity > 10uM) with molecules that had no structural similarity to any known inhibitor. Peptide to non peptide becomes a reality.