Effects of disulfide bridges and backbone connectivity on water sorption by protein matrices

Abstract Understanding the water sorption behavior of protein powders is important in applications such as the preservation of protein-based pharmaceuticals. Most globular proteins exhibit a characteristic sigmoidal water adsorption isotherm at ambient conditions. However, it is not well understood...

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Autores principales:	Sang Beom Kim, Rakesh S. Singh, Prem K. C. Paul, Pablo G. Debenedetti
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3515ff3e8ea345ea908c4aac632319cf
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spelling	oai:doaj.org-article:3515ff3e8ea345ea908c4aac632319cf2021-12-02T16:06:14ZEffects of disulfide bridges and backbone connectivity on water sorption by protein matrices10.1038/s41598-017-08561-22045-2322https://doaj.org/article/3515ff3e8ea345ea908c4aac632319cf2017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08561-2https://doaj.org/toc/2045-2322Abstract Understanding the water sorption behavior of protein powders is important in applications such as the preservation of protein-based pharmaceuticals. Most globular proteins exhibit a characteristic sigmoidal water adsorption isotherm at ambient conditions. However, it is not well understood how water sorption behavior is influenced by intrinsic factors that are related to structural properties of proteins. We investigate computationally how structural constraints on proteins influence the water sorption isotherms of amorphous protein powders. Specifically, we study the effects of non-local disulfide linkages and backbone connectivity using pheromone ER-23 and lysozyme as model proteins. We find that non-local disulfide linkages can significantly restrict structural changes during hydration and dehydration, and this in turn greatly reduces the extent of hysteresis between the adsorption and desorption branches. Upon removing the backbone connectivity by breaking all peptide bonds in lysozyme, we find that the hysteresis shifts towards the lower humidity regime, and the water uptake capacity is significantly enhanced. We attribute these changes to the higher aggregation propensity of the constraint-free amino acids in dehydrated condition, and the formation of a spanning water network at high hydration levels.Sang Beom KimRakesh S. SinghPrem K. C. PaulPablo G. DebenedettiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-9 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sang Beom Kim Rakesh S. Singh Prem K. C. Paul Pablo G. Debenedetti Effects of disulfide bridges and backbone connectivity on water sorption by protein matrices
description	Abstract Understanding the water sorption behavior of protein powders is important in applications such as the preservation of protein-based pharmaceuticals. Most globular proteins exhibit a characteristic sigmoidal water adsorption isotherm at ambient conditions. However, it is not well understood how water sorption behavior is influenced by intrinsic factors that are related to structural properties of proteins. We investigate computationally how structural constraints on proteins influence the water sorption isotherms of amorphous protein powders. Specifically, we study the effects of non-local disulfide linkages and backbone connectivity using pheromone ER-23 and lysozyme as model proteins. We find that non-local disulfide linkages can significantly restrict structural changes during hydration and dehydration, and this in turn greatly reduces the extent of hysteresis between the adsorption and desorption branches. Upon removing the backbone connectivity by breaking all peptide bonds in lysozyme, we find that the hysteresis shifts towards the lower humidity regime, and the water uptake capacity is significantly enhanced. We attribute these changes to the higher aggregation propensity of the constraint-free amino acids in dehydrated condition, and the formation of a spanning water network at high hydration levels.
format	article
author	Sang Beom Kim Rakesh S. Singh Prem K. C. Paul Pablo G. Debenedetti
author_facet	Sang Beom Kim Rakesh S. Singh Prem K. C. Paul Pablo G. Debenedetti
author_sort	Sang Beom Kim
title	Effects of disulfide bridges and backbone connectivity on water sorption by protein matrices
title_short	Effects of disulfide bridges and backbone connectivity on water sorption by protein matrices
title_full	Effects of disulfide bridges and backbone connectivity on water sorption by protein matrices
title_fullStr	Effects of disulfide bridges and backbone connectivity on water sorption by protein matrices
title_full_unstemmed	Effects of disulfide bridges and backbone connectivity on water sorption by protein matrices
title_sort	effects of disulfide bridges and backbone connectivity on water sorption by protein matrices
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/3515ff3e8ea345ea908c4aac632319cf
work_keys_str_mv	AT sangbeomkim effectsofdisulfidebridgesandbackboneconnectivityonwatersorptionbyproteinmatrices AT rakeshssingh effectsofdisulfidebridgesandbackboneconnectivityonwatersorptionbyproteinmatrices AT premkcpaul effectsofdisulfidebridgesandbackboneconnectivityonwatersorptionbyproteinmatrices AT pablogdebenedetti effectsofdisulfidebridgesandbackboneconnectivityonwatersorptionbyproteinmatrices
_version_	1718385079714054144

Effects of disulfide bridges and backbone connectivity on water sorption by protein matrices

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