title: Entropic contribution to the linking coefficient in fragment based drug design: a case study.
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.
authors.affiliation: Magnetic Resonance Center (CERM), University of Florence, Florence, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Borsi
authors.forename: Vito
authors.initials: V
authors.lastname: Calderone
authors.forename: Marco
authors.initials: M
authors.lastname: Fragai
authors.forename: Claudio
authors.initials: C
authors.lastname: Luchinat
authors.forename: Niko
authors.initials: N
authors.lastname: Sarti
mesh_terms: D002151:Calorimetry; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D015195:Drug Design; D019277:Entropy; D006877:Hydroxamic Acids / Q000737:chemistry*; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D053508:Matrix Metalloproteinase 12 / Q000737:chemistry*; D061965:Matrix Metalloproteinase Inhibitors; D008958:Models, Molecular; D011485:Protein Binding; D013449:Sulfonamides / Q000737:chemistry*
chemical_list: D006877:Hydroxamic Acids; D008024:Ligands; D061965:Matrix Metalloproteinase Inhibitors; D013449:Sulfonamides; C006358:acetohydroxamic acid; D053508:Matrix Metalloproteinase 12