The Privileged Chemical Space Predictor (PCSP): a computer program that identifies privileged chemical space from...

Modularly assembled combinatorial libraries are often used to identify ligands that bind to and modulate the function of a protein or a nucleic acid. Much of the data from screening these compounds, however, is not efficiently utilized to define structure-activity relationships (SAR). If SAR data are accurately constructed, it can enable the design of more potent binders. Herein, we describe a computer program called Privileged Chemical Space Predictor (PCSP) that statistically determines SAR from high-throughput screening (HTS) data and then identifies features in small molecules that predispose them for binding a target. Features are scored for statistical significance and can be utilized to design improved second generation compounds or more target-focused libraries. The program's utility is demonstrated through analysis of a modularly assembled peptoid library that previously was screened for binding to and inhibiting a group I intron RNA from the fungal pathogen Candida albicans.