Computational analysis of the amino acid interactions that promote or decrease protein solubility

Abstract The solubility of globular proteins is a basic biophysical property that is usually a prerequisite for their functioning. In this study, we probed the solubility of globular proteins with the help of the statistical potential formalism, in view of objectifying the connection of solubility w...

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Autores principales:	Qingzhen Hou, Raphaël Bourgeas, Fabrizio Pucci, Marianne Rooman
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Amino Acid Interactions Folding Free Energy Aggregation-prone Proteins Promote Protein Solubility Aliphatic Index Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3eac4e9330274cf091576e3224b564c9
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spelling	oai:doaj.org-article:3eac4e9330274cf091576e3224b564c92021-12-02T15:09:11ZComputational analysis of the amino acid interactions that promote or decrease protein solubility10.1038/s41598-018-32988-w2045-2322https://doaj.org/article/3eac4e9330274cf091576e3224b564c92018-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-32988-whttps://doaj.org/toc/2045-2322Abstract The solubility of globular proteins is a basic biophysical property that is usually a prerequisite for their functioning. In this study, we probed the solubility of globular proteins with the help of the statistical potential formalism, in view of objectifying the connection of solubility with structural and energetic properties and of the solubility-dependence of specific amino acid interactions. We started by setting up two independent datasets containing either soluble or aggregation-prone proteins with known structures. From these two datasets, we computed solubility-dependent distance potentials that are by construction biased towards the solubility of the proteins from which they are derived. Their analysis showed the clear preference of amino acid interactions such as Lys-containing salt bridges and aliphatic interactions to promote protein solubility, whereas others such as aromatic, His-π, cation-π, amino-π and anion-π interactions rather tend to reduce it. These results indicate that interactions involving delocalized π-electrons favor aggregation, unlike those involving no (or few) dispersion forces. Furthermore, using our potentials derived from either highly or weakly soluble proteins to compute protein folding free energies, we found that the difference between these two energies correlates better with solubility than other properties analyzed before such as protein length, isoelectric point and aliphatic index. This is, to the best of our knowledge, the first comprehensive in silico study of the impact of residue-residue interactions on protein solubility properties.The results of this analysis provide new insights that will facilitate future rational protein design applications aimed at modulating the solubility of targeted proteins.Qingzhen HouRaphaël BourgeasFabrizio PucciMarianne RoomanNature PortfolioarticleAmino Acid InteractionsFolding Free EnergyAggregation-prone ProteinsPromote Protein SolubilityAliphatic IndexMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-13 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Amino Acid Interactions Folding Free Energy Aggregation-prone Proteins Promote Protein Solubility Aliphatic Index Medicine R Science Q
spellingShingle	Amino Acid Interactions Folding Free Energy Aggregation-prone Proteins Promote Protein Solubility Aliphatic Index Medicine R Science Q Qingzhen Hou Raphaël Bourgeas Fabrizio Pucci Marianne Rooman Computational analysis of the amino acid interactions that promote or decrease protein solubility
description	Abstract The solubility of globular proteins is a basic biophysical property that is usually a prerequisite for their functioning. In this study, we probed the solubility of globular proteins with the help of the statistical potential formalism, in view of objectifying the connection of solubility with structural and energetic properties and of the solubility-dependence of specific amino acid interactions. We started by setting up two independent datasets containing either soluble or aggregation-prone proteins with known structures. From these two datasets, we computed solubility-dependent distance potentials that are by construction biased towards the solubility of the proteins from which they are derived. Their analysis showed the clear preference of amino acid interactions such as Lys-containing salt bridges and aliphatic interactions to promote protein solubility, whereas others such as aromatic, His-π, cation-π, amino-π and anion-π interactions rather tend to reduce it. These results indicate that interactions involving delocalized π-electrons favor aggregation, unlike those involving no (or few) dispersion forces. Furthermore, using our potentials derived from either highly or weakly soluble proteins to compute protein folding free energies, we found that the difference between these two energies correlates better with solubility than other properties analyzed before such as protein length, isoelectric point and aliphatic index. This is, to the best of our knowledge, the first comprehensive in silico study of the impact of residue-residue interactions on protein solubility properties.The results of this analysis provide new insights that will facilitate future rational protein design applications aimed at modulating the solubility of targeted proteins.
format	article
author	Qingzhen Hou Raphaël Bourgeas Fabrizio Pucci Marianne Rooman
author_facet	Qingzhen Hou Raphaël Bourgeas Fabrizio Pucci Marianne Rooman
author_sort	Qingzhen Hou
title	Computational analysis of the amino acid interactions that promote or decrease protein solubility
title_short	Computational analysis of the amino acid interactions that promote or decrease protein solubility
title_full	Computational analysis of the amino acid interactions that promote or decrease protein solubility
title_fullStr	Computational analysis of the amino acid interactions that promote or decrease protein solubility
title_full_unstemmed	Computational analysis of the amino acid interactions that promote or decrease protein solubility
title_sort	computational analysis of the amino acid interactions that promote or decrease protein solubility
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/3eac4e9330274cf091576e3224b564c9
work_keys_str_mv	AT qingzhenhou computationalanalysisoftheaminoacidinteractionsthatpromoteordecreaseproteinsolubility AT raphaelbourgeas computationalanalysisoftheaminoacidinteractionsthatpromoteordecreaseproteinsolubility AT fabriziopucci computationalanalysisoftheaminoacidinteractionsthatpromoteordecreaseproteinsolubility AT mariannerooman computationalanalysisoftheaminoacidinteractionsthatpromoteordecreaseproteinsolubility
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Computational analysis of the amino acid interactions that promote or decrease protein solubility

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