Entropic Contribution to the Linking Coefficient in Fragment Based Drug Design: A Case Study
Valentina Borsi, V. Calderone, Marco Fragai, Claudio Luchinat, Niko Sarti · Journal of Medicinal Chemistry · 2010
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.