1. Entropic contribution to the linking coefficient in fragment based drug design: a case study
- Author
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Niko Sarti, Valentina Borsi, Claudio Luchinat, Vito Calderone, and Marco Fragai
- Subjects
Models, Molecular ,Sulfonamides ,Magnetic Resonance Spectroscopy ,Stereochemistry ,Chemistry ,Entropy ,Calorimetry ,Matrix Metalloproteinase Inhibitors ,Crystallography, X-Ray ,Hydroxamic Acids ,Ligands ,Dissociation constant ,Weak binding ,Fragment (logic) ,Chemical physics ,Catalytic Domain ,Drug Design ,Matrix Metalloproteinase 12 ,Drug Discovery ,Molecular Medicine ,Protein Binding - Abstract
For several drug leads obtained by tethering weak binding ligands, the dissociation constant is smaller than the product of those of the individual fragments by a factor named the linking coefficient, E. This favorable contribution is attributed to the entropic gain that is realized when two weak binding ligands are tethered. Here we show a case study where the linking coefficient is strikingly small (E = 2.1 x 10(-3) M(-1)) and its totally entropic nature is demonstrated.
- Published
- 2010