An analysis of the binding of related ligands

✍ Scribed by H.P. Rappaport

• Publisher: Elsevier Science
• Year: 1976
• Tongue: English
• Weight: 797 KB
• Volume: 58
• Category: Article
• ISSN: 0022-5193
• DOI: 10.1016/s0022-5193(76)80119-1

✦ Synopsis

The thermodynamic relationship between the binding of the ligand, A-B, and analogs of its groups, A-X and B-Y, to a protein is derived using a thermodynamic cycle. Using the formalism, thermodynamic data, and simple models the following conclusions are reached:

(1) A significant free energy barrier exists against a ligand and a protein coming together. The free energy barrier is essential for understanding the specificity of ligand binding.

(2) In general the free energy of binding A-B is not equal to the sum of the free energies of binding A-H and B-H when A and B contribute independently to the binding of A-B.

(3) It is physically possible for a methyl group to make a contribution greater than 2.3 kcal/mol to the binding of a ligand without an autosteric mechanism.

(4) It is physically possible for tyrosine to bind at least 3.9 kcal/mol more strongly than phenylalanine if the hydroxyl group of tyrosine displaces a bound water molecule.

(5) The co-operative interactions due to the joint presence of the protonated amino and carboxylate groups in the zwitter ion of an amino acid can make significant contributions tb binding.