Dynamics of Hydration Water Plays a Key Role in Determining the Binding Thermodynamics of Protein Complexes

Abstract Interfacial waters are considered to play a crucial role in protein–protein interactions, but in what sense and why are they important? Here, using molecular dynamics simulations and statistical thermodynamic analyses, we demonstrate distinctive dynamic characteristics of the interfacial wa...

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Autores principales:	Song-Ho Chong, Sihyun Ham
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d2dbd5810ca14e038db625d3ffc14253
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spelling	oai:doaj.org-article:d2dbd5810ca14e038db625d3ffc142532021-12-02T15:06:13ZDynamics of Hydration Water Plays a Key Role in Determining the Binding Thermodynamics of Protein Complexes10.1038/s41598-017-09466-w2045-2322https://doaj.org/article/d2dbd5810ca14e038db625d3ffc142532017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-09466-whttps://doaj.org/toc/2045-2322Abstract Interfacial waters are considered to play a crucial role in protein–protein interactions, but in what sense and why are they important? Here, using molecular dynamics simulations and statistical thermodynamic analyses, we demonstrate distinctive dynamic characteristics of the interfacial water and investigate their implications for the binding thermodynamics. We identify the presence of extraordinarily slow (~1,000 times slower than in bulk water) hydrogen-bond rearrangements in interfacial water. We rationalize the slow rearrangements by introducing the “trapping” free energies, characterizing how strongly individual hydration waters are captured by the biomolecular surface, whose magnitude is then traced back to the number of water–protein hydrogen bonds and the strong electrostatic field produced at the binding interface. We also discuss the impact of the slow interfacial waters on the binding thermodynamics. We find that, as expected from their slow dynamics, the conventional approach to the water-mediated interaction, which assumes rapid equilibration of the waters’ degrees of freedom, is inadequate. We show instead that an explicit treatment of the extremely slow interfacial waters is critical. Our results shed new light on the role of water in protein–protein interactions, highlighting the need to consider its dynamics to improve our understanding of biomolecular bindings.Song-Ho ChongSihyun HamNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Song-Ho Chong Sihyun Ham Dynamics of Hydration Water Plays a Key Role in Determining the Binding Thermodynamics of Protein Complexes
description	Abstract Interfacial waters are considered to play a crucial role in protein–protein interactions, but in what sense and why are they important? Here, using molecular dynamics simulations and statistical thermodynamic analyses, we demonstrate distinctive dynamic characteristics of the interfacial water and investigate their implications for the binding thermodynamics. We identify the presence of extraordinarily slow (~1,000 times slower than in bulk water) hydrogen-bond rearrangements in interfacial water. We rationalize the slow rearrangements by introducing the “trapping” free energies, characterizing how strongly individual hydration waters are captured by the biomolecular surface, whose magnitude is then traced back to the number of water–protein hydrogen bonds and the strong electrostatic field produced at the binding interface. We also discuss the impact of the slow interfacial waters on the binding thermodynamics. We find that, as expected from their slow dynamics, the conventional approach to the water-mediated interaction, which assumes rapid equilibration of the waters’ degrees of freedom, is inadequate. We show instead that an explicit treatment of the extremely slow interfacial waters is critical. Our results shed new light on the role of water in protein–protein interactions, highlighting the need to consider its dynamics to improve our understanding of biomolecular bindings.
format	article
author	Song-Ho Chong Sihyun Ham
author_facet	Song-Ho Chong Sihyun Ham
author_sort	Song-Ho Chong
title	Dynamics of Hydration Water Plays a Key Role in Determining the Binding Thermodynamics of Protein Complexes
title_short	Dynamics of Hydration Water Plays a Key Role in Determining the Binding Thermodynamics of Protein Complexes
title_full	Dynamics of Hydration Water Plays a Key Role in Determining the Binding Thermodynamics of Protein Complexes
title_fullStr	Dynamics of Hydration Water Plays a Key Role in Determining the Binding Thermodynamics of Protein Complexes
title_full_unstemmed	Dynamics of Hydration Water Plays a Key Role in Determining the Binding Thermodynamics of Protein Complexes
title_sort	dynamics of hydration water plays a key role in determining the binding thermodynamics of protein complexes
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/d2dbd5810ca14e038db625d3ffc14253
work_keys_str_mv	AT songhochong dynamicsofhydrationwaterplaysakeyroleindeterminingthebindingthermodynamicsofproteincomplexes AT sihyunham dynamicsofhydrationwaterplaysakeyroleindeterminingthebindingthermodynamicsofproteincomplexes
_version_	1718388543758270464

Dynamics of Hydration Water Plays a Key Role in Determining the Binding Thermodynamics of Protein Complexes

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