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dc.contributor.author
Albano, Juan Manuel Ricardo
dc.contributor.author
Mussini, Nahuel
dc.contributor.author
Toriano, Roxana Mabel
dc.contributor.author
Facelli, Julio C.
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Ferraro, Marta Beatriz
dc.contributor.author
Pickholz, Mónica Andrea
dc.date.available
2019-10-17T13:48:29Z
dc.date.issued
2018-12
dc.identifier.citation
Albano, Juan Manuel Ricardo; Mussini, Nahuel; Toriano, Roxana Mabel; Facelli, Julio C.; Ferraro, Marta Beatriz; et al.; Calcium interactions with Cx26 hemmichannel: Spatial association between MD simulations biding sites and variant pathogenicity; Elsevier; Computational Biology And Chemistry; 77; 12-2018; 331-342
dc.identifier.issn
1476-9271
dc.identifier.uri
http://hdl.handle.net/11336/86139
dc.description.abstract
Connexinophaties are a collective of diseases related to connexin channels and hemichannels. In particular many Cx26 alterations are strongly associated to human deafness. Calcium plays an important role on this structures regulation. Here, using calcium as a probe, extensive atomistic Molecular Dynamics simulations were performed on the Cx26 hemichannel embedded in a lipid bilayer. Exploring different initial conditions and calcium concentration, simulation reached ∼4 μs. Several analysis were carried out in order to reveal the calcium distribution and localization, such as electron density profiles, density maps and distance time evolution, which is directly associated to the interaction energy. Specific amino acid interactions with calcium and their stability were capture within this context. Few of these sites such as, GLU42, GLU47, GLY45 and ASP50, were already suggested in the literature. Besides, we identified novel calcium biding sites: ASP2, ASP117, ASP159, GLU114, GLU119, GLU120 and VAL226. To the best of our knowledge, this is the first time that these sites are reported within this context. Furthermore, since various pathologies involving the Cx26 hemichannel are associated with pathogenic variants in the corresponding CJB2 gene, using ClinVar, we were able to spatially associate the 3D positions of the identified calcium binding sites within the framework of this work with reported pathogenic variants in the CJB2 gene. This study presents a first step on finding associations between molecular features and pathological variants of the Cx26 hemichannel.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Elsevier
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
CONNEXIN
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MOLECULAR DYNAMICS
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POPC
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VARIANT ANNOTATION
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Biofísica
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Ciencias Biológicas
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CIENCIAS NATURALES Y EXACTAS
dc.title
Calcium interactions with Cx26 hemmichannel: Spatial association between MD simulations biding sites and variant pathogenicity
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2019-10-16T18:26:44Z
dc.journal.volume
77
dc.journal.pagination
331-342
dc.journal.pais
Países Bajos
dc.journal.ciudad
Amsterdam
dc.description.fil
Fil: Albano, Juan Manuel Ricardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Nanobiotecnología. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Nanobiotecnología; Argentina
dc.description.fil
Fil: Mussini, Nahuel. Universidad de Buenos Aires; Argentina
dc.description.fil
Fil: Toriano, Roxana Mabel. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Ciencias Fisiológicas. Laboratorio de Biomembranas; Argentina
dc.description.fil
Fil: Facelli, Julio C.. University of Utah; Estados Unidos
dc.description.fil
Fil: Ferraro, Marta Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física de Buenos Aires; Argentina
dc.description.fil
Fil: Pickholz, Mónica Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Nanobiotecnología. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Nanobiotecnología; Argentina
dc.journal.title
Computational Biology And Chemistry
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/https://doi.org/10.1016/j.compbiolchem.2018.11.004
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