Protein Flexibility and Conformational Entropy in Ligand Binding Targeting the Carbohydrate Recognition Domain of Galectin-3
Drug design is predicated on knowledge of the three-dimensional structure of the protein-ligand complex and the thermodynamics of ligand binding. In the proposal for IN16B BATS mode we suggest to investigate the effect of ligand binding on the molecular dynamics of galectin-3 (Gal3C) using QENS. We propose to investigate the effects of three ligands on the dynamics of Gal3C: lactose (lac) and two synthetic high affinity inhibitors L2 and L3. Based on NMR changes of conformational entropy of the protein backbone DeltaS_bb and protein side-chains DeltaS_ss have been estimated for the three ligands. We suggest to investigate using QENS perturbation of internal relaxation rates and amplitudes of motion of Gal3C by ligand binding on the ps to ns time scale. From the determined amplitudes of motion, we will calculate conformational entropy changes of Gal3C upon ligand binding. We would like to make a quantitative comparison between QENS and already available NMR, ITC and X-ray crystallography data to obtain a better picture of the role of ligand binding for the dynamics of Gal3C, and to establish QENS as a quantitative tool for the study of protein-ligand binding.
Please note that you will need to login with your ILL credentials to download the data.
Download DataThe recommended format for citing this dataset in a research publication is in the following format:
Andreas M. Stadler; AKKE Mikael; APPEL Markus; GRAF VON WESTARP Igor; HARIS Luman and SEYDEL Tilo. (2021). Protein Flexibility and Conformational Entropy in Ligand Binding Targeting the Carbohydrate Recognition Domain of Galectin-3. Institut Laue-Langevin (ILL) doi:10.5291/ILL-DATA.8-04-917
ILL has partnered with DataCite as the registration agency
for data persistent identifiers.