Intriguing role of water in protein-ligand binding studied by neutron crystallography on trypsin complexes.

ABSTRACT: Hydrogen bonds are key interactions determining protein-ligand binding affinity and therefore fundamental to any biological process. Unfortunately, explicit structural information about hydrogen positions and thus H-bonds in protein-ligand complexes is extremely rare and similarly the important role of water during binding remains poorly understood. Here, we report on neutron structures of trypsin determined at very high resolutions ≤1.5 Å in uncomplexed and inhibited state complemented by X-ray and thermodynamic data and computer simulations. Our structures show the precise geometry of H-bonds between protein and the inhibitors N-amidinopiperidine and benzamidine along with the dynamics of the residual solvation pattern. Prior to binding, the ligand-free binding pocket is occupied by wate

SUBMITTER: Schiebel J 

PROVIDER: S-EPMC6120877 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature