Cargando…
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...
Autores principales: | , , , , |
---|---|
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 |
_version_ | 1783306795185340416 |
---|---|
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. |
format | Online Article Text |
id | pubmed-5853690 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT rayanushka acomputationalapproachforunderstandingtheinteractionsbetweengrapheneoxideandnucleosidediphosphatekinasewithimplicationsforheartfailure AT macwanisaac acomputationalapproachforunderstandingtheinteractionsbetweengrapheneoxideandnucleosidediphosphatekinasewithimplicationsforheartfailure AT singhshrishti acomputationalapproachforunderstandingtheinteractionsbetweengrapheneoxideandnucleosidediphosphatekinasewithimplicationsforheartfailure AT silwalsushila acomputationalapproachforunderstandingtheinteractionsbetweengrapheneoxideandnucleosidediphosphatekinasewithimplicationsforheartfailure AT patraprabir acomputationalapproachforunderstandingtheinteractionsbetweengrapheneoxideandnucleosidediphosphatekinasewithimplicationsforheartfailure AT rayanushka computationalapproachforunderstandingtheinteractionsbetweengrapheneoxideandnucleosidediphosphatekinasewithimplicationsforheartfailure AT macwanisaac computationalapproachforunderstandingtheinteractionsbetweengrapheneoxideandnucleosidediphosphatekinasewithimplicationsforheartfailure AT singhshrishti computationalapproachforunderstandingtheinteractionsbetweengrapheneoxideandnucleosidediphosphatekinasewithimplicationsforheartfailure AT silwalsushila computationalapproachforunderstandingtheinteractionsbetweengrapheneoxideandnucleosidediphosphatekinasewithimplicationsforheartfailure AT patraprabir computationalapproachforunderstandingtheinteractionsbetweengrapheneoxideandnucleosidediphosphatekinasewithimplicationsforheartfailure |