The Privileged Chemical Space Predictor (PCSP): a computer program that identifies privileged chemical space from screens of modularly assembled chemical libraries.
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.
Seedhouse
Steven J
SJ
Department of Chemistry and The Center of Excellence in Bioinformatics and Life Sciences, University at Buffalo, The State University of New York, 657 Natural Sciences Complex, Buffalo, NY 14260, USA.
Labuda
Lucas P
LP
Disney
Matthew D
MD
D002176:Candida albicans / Q000187:drug effects; D020650:Combinatorial Chemistry Techniques; D003198:Computer Simulation; D004247:DNA / Q000378:metabolism*; D015195:Drug Design; D020128:Inhibitory Concentration 50; D008024:Ligands; D015394:Molecular Structure; D019151:Peptide Library; D011485:Protein Binding; D054852:Small Molecule Libraries / Q000737:chemistry* / Q000494:pharmacology*; D012984:Software; D013329:Structure-Activity Relationship
D008024:Ligands; D019151:Peptide Library; D054852:Small Molecule Libraries; D004247:DNA