Exploration of Interfacial Hydration Networks of Target-Ligand Complexes

Norbert Jeszenoi, Mónika Bálint, István Horváth, David Van Der Spoel, C. Hetényi

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Interfacial 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.

Original languageEnglish
Pages (from-to)148-158
Number of pages11
JournalJournal of Chemical Information and Modeling
Volume56
Issue number1
DOIs
Publication statusPublished - Jan 25 2016

Fingerprint

Hydration
Ligands
water
Water
Proteins
drug
Histones
Molecules
biochemistry
networking
integrity
Biochemistry
Biomolecules
GTP-Binding Proteins
Pharmaceutical Preparations
Modulators
Peptides
regulation
Chromatin
interaction

ASJC Scopus subject areas

  • Chemistry(all)
  • Chemical Engineering(all)
  • Computer Science Applications
  • Library and Information Sciences

Cite this

Exploration of Interfacial Hydration Networks of Target-Ligand Complexes. / Jeszenoi, Norbert; Bálint, Mónika; Horváth, István; Van Der Spoel, David; Hetényi, C.

In: Journal of Chemical Information and Modeling, Vol. 56, No. 1, 25.01.2016, p. 148-158.

Research output: Contribution to journalArticle

Jeszenoi, Norbert ; Bálint, Mónika ; Horváth, István ; Van Der Spoel, David ; Hetényi, C. / Exploration of Interfacial Hydration Networks of Target-Ligand Complexes. In: Journal of Chemical Information and Modeling. 2016 ; Vol. 56, No. 1. pp. 148-158.
@article{941584c36297481483fc996b7d5bea9d,
title = "Exploration of Interfacial Hydration Networks of Target-Ligand Complexes",
abstract = "Interfacial 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.",
author = "Norbert Jeszenoi and M{\'o}nika B{\'a}lint and Istv{\'a}n Horv{\'a}th and {Van Der Spoel}, David and C. Het{\'e}nyi",
year = "2016",
month = "1",
day = "25",
doi = "10.1021/acs.jcim.5b00638",
language = "English",
volume = "56",
pages = "148--158",
journal = "Journal of Chemical Information and Modeling",
issn = "1549-9596",
publisher = "American Chemical Society",
number = "1",

}

TY - JOUR

T1 - Exploration of Interfacial Hydration Networks of Target-Ligand Complexes

AU - Jeszenoi, Norbert

AU - Bálint, Mónika

AU - Horváth, István

AU - Van Der Spoel, David

AU - Hetényi, C.

PY - 2016/1/25

Y1 - 2016/1/25

N2 - Interfacial 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.

AB - Interfacial 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.

UR - http://www.scopus.com/inward/record.url?scp=84956652987&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84956652987&partnerID=8YFLogxK

U2 - 10.1021/acs.jcim.5b00638

DO - 10.1021/acs.jcim.5b00638

M3 - Article

VL - 56

SP - 148

EP - 158

JO - Journal of Chemical Information and Modeling

JF - Journal of Chemical Information and Modeling

SN - 1549-9596

IS - 1

ER -