Model for computational drug discovery

In Silico Screening  

  • Protein structure-based high-throughput docking
  • Small molecule compound selection through pharmacophore, substructure and similarity searching
  • Availability of in silico libraries containing millions of accessible compounds

Protein Structure Function Target Assessment and Discovery Design

  • Protein target X-ray structure analysis, evaluation, planning and deployment for drug discovery and optimization studies
  • Generation of X-ray and homology based models of protein targets

Small Molecule Drug Discovery and Design

  • Hit identification, optimization, through all stages of lead and drug design modeling activities
  • Identification of novel scaffolds, enhancement of existing compound activity and properties, and maintenance of patentability

State of the art Computational Chemistry Resource

  • Extensive hardware base including High-Performance-Computing (HPC) capabilities, high-end 3-D graphics workstations and extensive storage facilities
  • Robust suites of protein and small molecule tools for computational studies including protein analysis, homology modeling, ligand and protein based in silico screening, pharmacophore modeling, chemical informatics, property prediction and visualization


Robotic Drug Screening

Biochemical assays for Multiple Targets    

  • Proven track record with Kinases, phosphatases, proteases,lipid metabolic enzymes, epigenetic enzymes, ubiquitinautophagy and SUMO related enzymes,
  • Ligand/receptor, DNA/protein and protein/protein interaction

Focused library screens and hit confirmation

Manage and outsource HTS activities

Support project in Hit to Lead (H2L) and Lead Optimization (LO) Phases

Testing of H2L and LO compounds

  • primary
  • secondary
  • selectivity/profiling assays

Support of Hit Validation

  • Development of compound binding assaysthermal shift or other binding assays
  • Mechanism of action studies for enzyme kinetics, compound reversibility


HTS Hit Validation: Protein – Drug Binding

  • Confirmation that drugs (hits) discovered from robotic screening bind specifically to protein target using several different orthogonal (secondary) assays
  • Elucidate binding affinity of inhibitors/ligands

Hit to Lead / Lead Optimization / Mechanism of Action

  • Determine mechanism of action (MOA) for lead small molecule inhibitors/ligands
    • Competitive, non-competitive, uncompetitive; reversible/irreversible
    • Kinetics of binding (kon, koff)
  • Establish consistent structure activity relationship (SAR) per class of compounds
  • Characterize thermodynamics and stoichiometry of binding

Protein Characterization

  • Measure the affinity and kinetics of ligand / drug binding to proteins / DNA by Surface Plasmon Resonance (SensiQ Pioneer)
  • Evaluate protein fold by measuring secondary structure content using circular dichroism
    • wild type vs. mutant protein constructs
  • Determine protein structural stability and ligand binding affinity using thermal shift protein melting methods (Thermofluor or CD)
  • Applications: proteases, polymerases, cytokines, transferases, kinases, scaffolding proteins, etc.

Characterization of Base Pairing for DNA/RNA and Lipid Interactions

Biophysical Chemical Instruments

  • • SensiQ Surface Plasmon Resonance, Jasco J810 CD Spectropolarimeter, QuantStudio 5 qPCR, Spectromax Gemini fluorescence, Spectromax 384 Plus absorbance & Envision plate readers.


DNA helix

DNA construct design

  • Gene synthesis and codon optimizationFrom sequence or accession number
  • For increase protein expression

Gene cloning and mutagenesis

Research grade DNA preparation

  • mini, midi, maxi and giga scale
  • Robotic preps for 96-well high throughput [HTP] studies


Scientist cell culturing

E. Coli

  • Screening for optimal expression yields and protein solubility using various bacterial hosts
  • Small to bulk scale up

Insect Cells

  • Recombinant Baculovirus production and titration
  • Expression screening and optimization inSf9, Sf21,H5cells

Mammalian Cells

  • Adherent and suspension cell culture
  • Expression screening and optimization (HEK, CHO)
  • Transient and stable transfection
  • Stable cell line generation


Equipment for protein production and purification

Expression Optimization

  • Routine testing of multiple expression/induction conditions to optimize protein expression
  • Analysts by SDS-PAGE and Western Blot of crude, soluble and pull down fractions

Protein Purification

  • Pilot to bulk scale
  • Endogenous and recombinant protein production
  • Protein refolding from inclusion bodies
  • Biochemical and biophysical assay grade purity
  • Protease cleavage of fusion and purification tags
  • Affinity tag and enzymatic modifications for assay development
  • 15N labeling for structural determination by NMR

Quality Control/ Analytics

  • Analytical SEC
  • Static light scattering
  • Western blot
  • Activity Assays
  • Mass spectrometry of whole protein

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