Protein flexibility and conformational entropy in ligand design targeting the carbohydrate recognition domain of galectin-3.

ABSTRACT: Rational drug design is predicated on knowledge of the three-dimensional structure of the protein-ligand complex and the thermodynamics of ligand binding. Despite the fundamental importance of both enthalpy and entropy in driving ligand binding, the role of conformational entropy is rarely addressed in drug design. In this work, we have probed the conformational entropy and its relative contribution to the free energy of ligand binding to the carbohydrate recognition domain of galectin-3. Using a combination of NMR spectroscopy, isothermal titration calorimetry, and X-ray crystallography, we characterized the binding of three ligands with dissociation constants ranging over 2 orders of magnitude. (15)N and (2)H spin relaxation measurements showed that the protein backbone and side chains r

SUBMITTER: Diehl C 

PROVIDER: S-EPMC2954529 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature