Calorimetry as a Tool to Assist in Target Characterization, Drug Lead Discovery and Optimization

biomolecular_analysis_1A cooperative 3-dimensional structure is essential to a protein's biological function, The molecular mechanism through which a protein carries out its function can be modulated by the presence of domains and subunits, and the extent of molecular "communication" between these structural units. It is the energetic consequences and not the structural architecture, per se, that affects the mechanism and which can be quantified by a thermodynamic analysis. The long term goal of protein structural thermodynamics is the ability to predict the (1) energetics, (2) stability, (3) ligand affinity, and (4) relative and absolute importance of protein and ligand functional groups. There is considerable experimental data to support this concept that comes from the detailed analyses in two areas, namely, protein stability and protein ligand interactions. Calorimetry is a unique and powerful technique that can be used to determine all the relevant thermodynamic parameters needed to correlate structure with energetics.

Knowledge of how the thermodynamic parameters of binding vary with different lead structures and chemical analogs can direct the choices for further chemical modification. The CBSE Biomolecular Analysis Group currently uses biocalorimetry data and other biophysical tools to enhance the design and optimization of lead compounds.

Isothermal Titration Calorimetry and Differential Scanning Calorimetry can advance your research with applications in

  • Protein Engineering; detect misfolded domains
  • Proteomics: energetic domain architecture
  • Optimization of crystallization conditions
  • Biopharmaceutical Formulations
  • Drug Discovery: universal assay for lead identification, development and understanding the importance of functional groups, salvation, hydrophobicity and conformation