Conformation–activity relationship explained

In biochemistry, the conformation–activity relationship is the relationship between the biological activity and the chemical structure or conformational changes of a biomolecule. This terminology emphasizes the importance of dynamic conformational changes for the biological function, rather than the importance of static three-dimensional structure used in the analysis of structure–activity relationships.[1]

The conformational changes usually take place during intermolecular association, such as protein–protein interaction or protein–ligand binding. A binding partner changes the conformation of a biomolecule (e.g. a protein) to enable or disable its biochemical activity.

Methods for analysis of conformation activity relationship vary from in silico[2] or using experimental methods such as X-ray crystallography and NMR where the conformation before and after activity can be compared statically or using dynamic methods such as multi-parametric surface plasmon resonance, dual-polarisation interferometry or circular dichroism where the kinetics as well as degree of conformational change can be quantified.

Experimental techniques

Static

Static experimental techniques include X-ray crystallography and NMR.

Dynamic

Dynamic experimental techniques include multi-parametric surface plasmon resonance, dual-polarization interferometry, and circular dichroism.

Notes and References

  1. Taylor. RE. Chen. Y. Beatty. A. Myles. DC. Zhou. Y. Conformation-activity relationships in polyketide natural products: a new perspective on the rational design of epothilone analogues. Journal of the American Chemical Society. 125. 1. 26–7. 2003. 12515494. 10.1021/ja028196l.
  2. Carotenuto. Alfonso. D'ursi. Anna Maria. Mulinacci. Barbara. Paolini. Ilaria. Lolli. Francesco. Papini. Anna Maria. Novellino. Ettore. Rovero. Paolo. Conformation−Activity Relationship of Designed Glycopeptides as Synthetic Probes for the Detection of Autoantibodies, Biomarkers of Multiple Sclerosis. Journal of Medicinal Chemistry. 49. 5072–9. 2006. 10.1021/jm060117j. 17. 16913697.