ci5b00638_si_003.zip (205.72 kB)
Exploration of Interfacial Hydration Networks of Target–Ligand Complexes
dataset
posted on 2016-01-25, 00:00 authored by Norbert Jeszenői, Mónika Bálint, István Horváth, David van der Spoel, Csaba HetényiInterfacial
hydration strongly influences interactions between
biomolecules. For example, drug–target complexes are often
stabilized by hydration networks formed between hydrophilic residues
and water molecules at the interface. Exhaustive exploration of hydration
networks is challenging for experimental as well as theoretical methods
due to high mobility of participating water molecules. In the present
study, we introduced a tool for determination of the complete, void-free
hydration structures of molecular interfaces. The tool was applied
to 31 complexes including histone proteins, a HIV-1 protease, a G-protein-signaling
modulator, and peptide ligands of various lengths. The complexes contained
344 experimentally determined water positions used for validation,
and excellent agreement with these was obtained. High-level cooperation
between interfacial water molecules was detected by a new approach
based on the decomposition of hydration networks into static and dynamic
network regions (subnets). Besides providing hydration structures
at the atomic level, our results uncovered hitherto hidden networking
fundaments of integrity and stability of complex biomolecular interfaces
filling an important gap in the toolkit of drug design and structural
biochemistry. The presence of continuous, static regions of the interfacial
hydration network was found necessary also for stable complexes of
histone proteins participating in chromatin assembly and epigenetic
regulation.