Conformation activity relationship

Conformation-activity relationship is the relationship between the biological activity and the conformation 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 dual polarisation interferometry or circular dichroism where the kinetics as well as degree of conformational change can be quantified.

Experimental techniques

Static

Dynamic

References

  1. ^ Taylor, RE; Chen, Y; Beatty, A; Myles, DC; Zhou, Y (2003). "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. doi:10.1021/ja028196l. PMID 12515494. 
  2. ^ Carotenuto, Alfonso; D'ursi, Anna Maria; Mulinacci, Barbara; Paolini, Ilaria; Lolli, Francesco; Papini, Anna Maria; Novellino, Ettore; Rovero, Paolo (2006). "Conformation−Activity Relationship of Designed Glycopeptides as Synthetic Probes for the Detection of Autoantibodies, Biomarkers of Multiple Sclerosis". Journal of Medicinal Chemistry 49 (17): 5072–9. doi:10.1021/jm060117j. PMID 16913697.