Assay Design

• Biochemical assays

• Cell-based assays

• Image-based assays

• Whole organism-based assays

NIH Chemical Genomics Assay Guidance Manual including a chapter on inhibition of protein-protein interactions by ECBDC Associate Director, Yuhong Du

High-Throughput Screening

Screening Systems

We have established multiple independent, parallel robotic systems for HTS/μHTS/iHTS and HCS operations that are capable of handling 96-, 384-, and 1536-well plate formats. These systems accommodate a variety of assay formats and are particularly well-suited for conventional and multiplex protein-protein interactions and phenotypic screens.

• HTS/HCS system I: The first system features a central vertical robotic system with three outpost readers: (i) EnVision multimode reader (HTS in 96/384/1536 well format), (ii) FlexStation II agonist-injectable, 384-well fluorescence reader, and (iii) ImageXpress (HCS in 96/384-well format). This system is integrated with a cell hotel, plate stacker, and various liquid handlers equipped with pin tools for low-volume (nL) transfer. All of these components are in an enclosed environment, facilitating live-cell HCS screens under aseptic conditions.

• HTS/HCS system II: The second system features the Twister II robot integrated with (i) an EnVision multimode reader (HTS in 96/384/1536-well format) and (ii) ImageXpress (HCS in 96/384/1536 well format) supported by the Sciclone liquid handling workstation.

• System III: Corning’s Epic system for label-free molecular interaction screens provides a third platform for hit identification and confirmation by direct detection of protein-compound binding and cell-based screens under physiological conditions.

Compound library collections

We have a collection of more than 500K chemical compounds, including:

• Bioactive compounds

• FDA approved drugs

• Natural products

• Diversity libraries

Informatics

High-throughput screening data analysis and management

• Data reduction and management

• Data presentation, result query

• Compound library management, plate managment

• File preprocessing, report preparation

• Chemical queries

Cheminformatics

• Cluster analysis and hit-prioritization

• Molecular property calculations and filtering

• PAINS and REOS compounds identification

• Quantitative Structure-Activity Relationship (QSAR)

• ADME properties prediction

Bioinformatics

• Integration and analysis of large-scale genomic datasets, including
  • NCI Genomic Data Commons
  • The Cancer Genome Atlas (TCGA)
  • Cancer Cell Line Encyclopedia (CCLE)
  • Project Achilles

• Analysis of gene co-expression and mutual exclusivity of genomic alterations

• Analysis of Protein-protein, protein-compound, and functional interaction networks topology

Molecular Modeling

• Protein homology modeling, analysis of secondary structure, and functional domains

• Molecular docking and virtual screening of compound libraries

• Protein-protein and protein-peptide docking

• Molecular dynamics simulation

• Structure-based and ligand-based drug design and structure optimization