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A Computational Approach for Understanding the Interactions between Graphene Oxide and Nucleoside Diphosphate Kinase with Implications for Heart Failure

During a heart failure, an increased content and activity of nucleoside diphosphate kinase (NDPK) in the sarcolemmal membrane is responsible for suppressing the formation of the second messenger cyclic adenosine monophosphate (cAMP)—a key component required for calcium ion homeostasis for the proper...

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Autores principales: Ray, Anushka, Macwan, Isaac, Singh, Shrishti, Silwal, Sushila, Patra, Prabir
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5853690/
https://www.ncbi.nlm.nih.gov/pubmed/29360759
http://dx.doi.org/10.3390/nano8020057
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author Ray, Anushka
Macwan, Isaac
Singh, Shrishti
Silwal, Sushila
Patra, Prabir
author_facet Ray, Anushka
Macwan, Isaac
Singh, Shrishti
Silwal, Sushila
Patra, Prabir
author_sort Ray, Anushka
collection PubMed
description During a heart failure, an increased content and activity of nucleoside diphosphate kinase (NDPK) in the sarcolemmal membrane is responsible for suppressing the formation of the second messenger cyclic adenosine monophosphate (cAMP)—a key component required for calcium ion homeostasis for the proper systolic and diastolic functions. Typically, this increased NDPK content lets the surplus NDPK react with a mutated G protein in the beta-adrenergic signal transduction pathway, thereby inhibiting cAMP synthesis. Thus, it is thus that inhibition of NDPK may cause a substantial increase in adenylate cyclase activity, which in turn may be a potential therapy for end-stage heart failure patients. However, there is little information available about the molecular events at the interface of NDPK and any prospective molecule that may potentially influence its reactive site (His118). Here we report a novel computational approach for understanding the interactions between graphene oxide (GO) and NDPK. Using molecular dynamics, it is found that GO interacts favorably with the His118 residue of NDPK to potentially prevent its binding with adenosine triphosphate (ATP), which otherwise would trigger the phosphorylation of the mutated G protein. Therefore, this will result in an increase in cAMP levels during heart failure.
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spelling pubmed-58536902018-03-16 A Computational Approach for Understanding the Interactions between Graphene Oxide and Nucleoside Diphosphate Kinase with Implications for Heart Failure Ray, Anushka Macwan, Isaac Singh, Shrishti Silwal, Sushila Patra, Prabir Nanomaterials (Basel) Article During a heart failure, an increased content and activity of nucleoside diphosphate kinase (NDPK) in the sarcolemmal membrane is responsible for suppressing the formation of the second messenger cyclic adenosine monophosphate (cAMP)—a key component required for calcium ion homeostasis for the proper systolic and diastolic functions. Typically, this increased NDPK content lets the surplus NDPK react with a mutated G protein in the beta-adrenergic signal transduction pathway, thereby inhibiting cAMP synthesis. Thus, it is thus that inhibition of NDPK may cause a substantial increase in adenylate cyclase activity, which in turn may be a potential therapy for end-stage heart failure patients. However, there is little information available about the molecular events at the interface of NDPK and any prospective molecule that may potentially influence its reactive site (His118). Here we report a novel computational approach for understanding the interactions between graphene oxide (GO) and NDPK. Using molecular dynamics, it is found that GO interacts favorably with the His118 residue of NDPK to potentially prevent its binding with adenosine triphosphate (ATP), which otherwise would trigger the phosphorylation of the mutated G protein. Therefore, this will result in an increase in cAMP levels during heart failure. MDPI 2018-01-23 /pmc/articles/PMC5853690/ /pubmed/29360759 http://dx.doi.org/10.3390/nano8020057 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ray, Anushka
Macwan, Isaac
Singh, Shrishti
Silwal, Sushila
Patra, Prabir
A Computational Approach for Understanding the Interactions between Graphene Oxide and Nucleoside Diphosphate Kinase with Implications for Heart Failure
title A Computational Approach for Understanding the Interactions between Graphene Oxide and Nucleoside Diphosphate Kinase with Implications for Heart Failure
title_full A Computational Approach for Understanding the Interactions between Graphene Oxide and Nucleoside Diphosphate Kinase with Implications for Heart Failure
title_fullStr A Computational Approach for Understanding the Interactions between Graphene Oxide and Nucleoside Diphosphate Kinase with Implications for Heart Failure
title_full_unstemmed A Computational Approach for Understanding the Interactions between Graphene Oxide and Nucleoside Diphosphate Kinase with Implications for Heart Failure
title_short A Computational Approach for Understanding the Interactions between Graphene Oxide and Nucleoside Diphosphate Kinase with Implications for Heart Failure
title_sort computational approach for understanding the interactions between graphene oxide and nucleoside diphosphate kinase with implications for heart failure
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5853690/
https://www.ncbi.nlm.nih.gov/pubmed/29360759
http://dx.doi.org/10.3390/nano8020057
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