Resources - Lead Discovery

Assay Development

Through the Biomolecular Screening and Drug Discovery facility, researchers can qualitatively assess or quantitatively measure the presence or amount or the functional activity of a target entity against a chemical library. Services include cell-based assays (robotic), noncell-based assays and testing of the efficiency of chemicals to targeted cells using fluorescence. Contact: Larisa Avramova, 765-496-3102 or lva@purdue.edu.

High-throughput Screening

The Biomolecular Screening and Drug Discovery facility enables researchers to conduct millions of tests rapidly in order to identify active compounds, antibodies or genes that modulate a particular biomolecular pathway. Contact: Larisa Avramova, 765-496-3102 or lva@purdue.edu.

Compound Libraries

The current compound collection of around 200,000 unique entities is assembled from commercial and synthetic libraries provided by on- and off-campus researchers. The current collection is composed of mostly drug-like compounds supplemented with natural products and synthetic intermediates. The compound libraries are owned by Andrew Mesecar, the Walther Professor of Cancer Structural Biology, and are currently available to researchers who wish to screen their assays against these libraries using the Bindley Biosciences Center Integrated Screening Facility. Contact: Sergey Savinov, ssavinov@purdue.edu, or Andrew Mesecar, amesecar@purdue.edu.

In Silico Screening

This resource supports computer-based virtual screening of both in-house and external compound collections through docking and other computational and modeling approaches. Bioassay data are analyzed in concert with cheminformatics approaches to propose likely binding arrangements and 3D pharmacophore maps. Homology models are generated, validated by SAR correlations, and utilized in modeling applications, including docking. Structure-guided and combinatorial compound-generation tools are used for hit-to-lead optimizations. Services include 3D pharmacophore modeling and screening, homology modeling, high-throughput virtual screening of in-house and external libraries, comparison of in-house libraries for hit density and structure-based design of novel drug candidates. The majority of the computational modeling work flow is accomplished via the Schrodinger program suite (LigPrep, Glide, CombiGlide, and Prime). Contact: Sergey Savinov, ssavinov@purdue.edu, or Andrew Mesecar, amesecar@purdue.edu.

Cheminformatics

The Cheminformatics resource supports compound management (registration, inventory, plate formatting and tracking), processing, analysis of HTS data, and data mining using both local and public databases. The Cheminformatics resource also supports SAR analysis of bioassay results, and, in conjunction with computational modeling approaches can propose likely binding arrangements of HTS hits and 3D pharmacophore maps. The 2D and 3D SAR results can be further utilized in small-molecule design for custom synthesis or commercial acquisition of follow-up compounds. Services include: The majority of the cheminformatics work flow is accomplished via the Dotmatics (Browser, Vortex, Pinpoint, Nucleus, Register, Studies) program suite. This fully integrated web-based cheminformatics platform automates the data processing from the compound information (structure, plate location, etc.) and assay results to the HTS data analysis, compound clustering and SAR exploration. An Oracle database, maintained by the Information Technology at Purdue University (ITaP), is utilized for Dotmatics data storage and rapid retrieval. In addition, Schrödinger’s Epik and QikProp programs are used to predict ADME properties in hit-to-lead optimizations. Contact: Sergey Savinov, ssavinov@purdue.edu, or Andrew Mesecar, amesecar@purdue.edu.