Resources - Lead Discovery
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 email@example.com.
High-throughput ScreeningThe 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 firstname.lastname@example.org.
Compound LibrariesThe 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, email@example.com, or Andrew Mesecar, firstname.lastname@example.org.
In Silico ScreeningThis 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).
- LigPrep generates reliable 3D models of ligands by including tautomeric, ionization, and stereochemical variations, as well as enabling use of flexible filters to allow generation of fully customizable ligand libraries for further computational analysis.
- Glide is a complete state-of-the-art solution to ligand–receptor docking from high processing capacity high-throughput virtual screening (HTVS) , capable of processing tens of millions of compounds, to minimization-enhanced docking, providing the highest degree of accuracy in binding poses.
- CombiGlide utilizes core-hopping technology and combinatorial docking algorithms and to design focused libraries and identify novel scaffolds.
- Prime, a fully integrated and customizable tool for accurate protein structure prediction, enables generation of reliable homology models and induced fit (flexible receptor) docking.
CheminformaticsThe 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:
- HTS data processing, analysis, and sharing
- Database data mining
- SAR analysis and development by integrated cheminformatics and docking approaches
- Design of follow-up compounds or libraries
- Identification of commercial sources for compounds of interest and analogs
- Screening data management, which allows creation, capture, analysis and storage of chemical, biological and ad hoc research data
- Epik is a robust tool for predicting pKa values and tautomerism in putative ligands
- QikProp predicts ADME properties of drug candidates