Forces and Disease: Electrostatic force differences caused by mutations in kinesin motor domains can distinguish between disease-causing and non-disease-causing mutations

Abstract The ability to predict if a given mutation is disease-causing or not has enormous potential to impact human health. Typically, these predictions are made by assessing the effects of mutation on macromolecular stability and amino acid conservation. Here we report a novel feature: the electro...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Lin Li, Zhe Jia, Yunhui Peng, Subash Godar, Ivan Getov, Shaolei Teng, Joshua Alper, Emil Alexov
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3244623306c548dabf75f515f8e670ca
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:3244623306c548dabf75f515f8e670ca
record_format	dspace
spelling	oai:doaj.org-article:3244623306c548dabf75f515f8e670ca2021-12-02T15:04:54ZForces and Disease: Electrostatic force differences caused by mutations in kinesin motor domains can distinguish between disease-causing and non-disease-causing mutations10.1038/s41598-017-08419-72045-2322https://doaj.org/article/3244623306c548dabf75f515f8e670ca2017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08419-7https://doaj.org/toc/2045-2322Abstract The ability to predict if a given mutation is disease-causing or not has enormous potential to impact human health. Typically, these predictions are made by assessing the effects of mutation on macromolecular stability and amino acid conservation. Here we report a novel feature: the electrostatic component of the force acting between a kinesin motor domain and tubulin. We demonstrate that changes in the electrostatic component of the binding force are able to discriminate between disease-causing and non-disease-causing mutations found in human kinesin motor domains using the receiver operating characteristic (ROC). Because diseases may originate from multiple effects not related to kinesin-microtubule binding, the prediction rate of 0.843 area under the ROC plot due to the change in magnitude of the electrostatic force alone is remarkable. These results reflect the dependence of kinesin’s function on motility along the microtubule, which suggests a precise balance of microtubule binding forces is required.Lin LiZhe JiaYunhui PengSubash GodarIvan GetovShaolei TengJoshua AlperEmil AlexovNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Lin Li Zhe Jia Yunhui Peng Subash Godar Ivan Getov Shaolei Teng Joshua Alper Emil Alexov Forces and Disease: Electrostatic force differences caused by mutations in kinesin motor domains can distinguish between disease-causing and non-disease-causing mutations
description	Abstract The ability to predict if a given mutation is disease-causing or not has enormous potential to impact human health. Typically, these predictions are made by assessing the effects of mutation on macromolecular stability and amino acid conservation. Here we report a novel feature: the electrostatic component of the force acting between a kinesin motor domain and tubulin. We demonstrate that changes in the electrostatic component of the binding force are able to discriminate between disease-causing and non-disease-causing mutations found in human kinesin motor domains using the receiver operating characteristic (ROC). Because diseases may originate from multiple effects not related to kinesin-microtubule binding, the prediction rate of 0.843 area under the ROC plot due to the change in magnitude of the electrostatic force alone is remarkable. These results reflect the dependence of kinesin’s function on motility along the microtubule, which suggests a precise balance of microtubule binding forces is required.
format	article
author	Lin Li Zhe Jia Yunhui Peng Subash Godar Ivan Getov Shaolei Teng Joshua Alper Emil Alexov
author_facet	Lin Li Zhe Jia Yunhui Peng Subash Godar Ivan Getov Shaolei Teng Joshua Alper Emil Alexov
author_sort	Lin Li
title	Forces and Disease: Electrostatic force differences caused by mutations in kinesin motor domains can distinguish between disease-causing and non-disease-causing mutations
title_short	Forces and Disease: Electrostatic force differences caused by mutations in kinesin motor domains can distinguish between disease-causing and non-disease-causing mutations
title_full	Forces and Disease: Electrostatic force differences caused by mutations in kinesin motor domains can distinguish between disease-causing and non-disease-causing mutations
title_fullStr	Forces and Disease: Electrostatic force differences caused by mutations in kinesin motor domains can distinguish between disease-causing and non-disease-causing mutations
title_full_unstemmed	Forces and Disease: Electrostatic force differences caused by mutations in kinesin motor domains can distinguish between disease-causing and non-disease-causing mutations
title_sort	forces and disease: electrostatic force differences caused by mutations in kinesin motor domains can distinguish between disease-causing and non-disease-causing mutations
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/3244623306c548dabf75f515f8e670ca
work_keys_str_mv	AT linli forcesanddiseaseelectrostaticforcedifferencescausedbymutationsinkinesinmotordomainscandistinguishbetweendiseasecausingandnondiseasecausingmutations AT zhejia forcesanddiseaseelectrostaticforcedifferencescausedbymutationsinkinesinmotordomainscandistinguishbetweendiseasecausingandnondiseasecausingmutations AT yunhuipeng forcesanddiseaseelectrostaticforcedifferencescausedbymutationsinkinesinmotordomainscandistinguishbetweendiseasecausingandnondiseasecausingmutations AT subashgodar forcesanddiseaseelectrostaticforcedifferencescausedbymutationsinkinesinmotordomainscandistinguishbetweendiseasecausingandnondiseasecausingmutations AT ivangetov forcesanddiseaseelectrostaticforcedifferencescausedbymutationsinkinesinmotordomainscandistinguishbetweendiseasecausingandnondiseasecausingmutations AT shaoleiteng forcesanddiseaseelectrostaticforcedifferencescausedbymutationsinkinesinmotordomainscandistinguishbetweendiseasecausingandnondiseasecausingmutations AT joshuaalper forcesanddiseaseelectrostaticforcedifferencescausedbymutationsinkinesinmotordomainscandistinguishbetweendiseasecausingandnondiseasecausingmutations AT emilalexov forcesanddiseaseelectrostaticforcedifferencescausedbymutationsinkinesinmotordomainscandistinguishbetweendiseasecausingandnondiseasecausingmutations
_version_	1718389007535046656

Forces and Disease: Electrostatic force differences caused by mutations in kinesin motor domains can distinguish between disease-causing and non-disease-causing mutations

Ejemplares similares