New insights into the microscopic interactions associated with the physical mechanism of action of highly diluted biologics

Abstract In this investigation, we report the effect on the microscopic dynamics and interactions of the cytokine interferon gamma (IFN-γ) and antibodies to IFN-γ (anti-IFN-γ) and to the interferon gamma receptor 1 (anti-IFNGR1) prepared in exceptionally dilute solutions of initial proteins. Using b...

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Autor principal: Kristina N. Woods
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Lenguaje:EN
Publicado: Nature Portfolio 2021
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Acceso en línea:https://doaj.org/article/0fb7f4bc74944d049a0ba23b214bd7f3
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spelling oai:doaj.org-article:0fb7f4bc74944d049a0ba23b214bd7f32021-12-02T16:31:47ZNew insights into the microscopic interactions associated with the physical mechanism of action of highly diluted biologics10.1038/s41598-021-93326-12045-2322https://doaj.org/article/0fb7f4bc74944d049a0ba23b214bd7f32021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-93326-1https://doaj.org/toc/2045-2322Abstract In this investigation, we report the effect on the microscopic dynamics and interactions of the cytokine interferon gamma (IFN-γ) and antibodies to IFN-γ (anti-IFN-γ) and to the interferon gamma receptor 1 (anti-IFNGR1) prepared in exceptionally dilute solutions of initial proteins. Using both THz spectroscopy and molecular dynamics simulations we have uncovered that the high dilution method of sample preparation results in the reorganization of the sample surface residue dynamics at the solvent–protein interface that leads to both structural and kinetic heterogeneous dynamics that ultimately create interactions that enhance the binding probability of the antigen binding site. Our results indicate that the modified interfacial dynamics of anti-IFN-γ and anti-IFGNR1 that we probe experimentally are directly associated with alterations in the complementarity regions of the distinct antibodies that designate both antigen–antibody affinity and recognition.Kristina N. WoodsNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-26 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Kristina N. Woods
New insights into the microscopic interactions associated with the physical mechanism of action of highly diluted biologics
description Abstract In this investigation, we report the effect on the microscopic dynamics and interactions of the cytokine interferon gamma (IFN-γ) and antibodies to IFN-γ (anti-IFN-γ) and to the interferon gamma receptor 1 (anti-IFNGR1) prepared in exceptionally dilute solutions of initial proteins. Using both THz spectroscopy and molecular dynamics simulations we have uncovered that the high dilution method of sample preparation results in the reorganization of the sample surface residue dynamics at the solvent–protein interface that leads to both structural and kinetic heterogeneous dynamics that ultimately create interactions that enhance the binding probability of the antigen binding site. Our results indicate that the modified interfacial dynamics of anti-IFN-γ and anti-IFGNR1 that we probe experimentally are directly associated with alterations in the complementarity regions of the distinct antibodies that designate both antigen–antibody affinity and recognition.
format article
author Kristina N. Woods
author_facet Kristina N. Woods
author_sort Kristina N. Woods
title New insights into the microscopic interactions associated with the physical mechanism of action of highly diluted biologics
title_short New insights into the microscopic interactions associated with the physical mechanism of action of highly diluted biologics
title_full New insights into the microscopic interactions associated with the physical mechanism of action of highly diluted biologics
title_fullStr New insights into the microscopic interactions associated with the physical mechanism of action of highly diluted biologics
title_full_unstemmed New insights into the microscopic interactions associated with the physical mechanism of action of highly diluted biologics
title_sort new insights into the microscopic interactions associated with the physical mechanism of action of highly diluted biologics
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/0fb7f4bc74944d049a0ba23b214bd7f3
work_keys_str_mv AT kristinanwoods newinsightsintothemicroscopicinteractionsassociatedwiththephysicalmechanismofactionofhighlydilutedbiologics
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