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dc.contributor.author
Vega Hissi, Esteban Gabriel
dc.contributor.author
Tosso, Rodrigo David
dc.contributor.author
Enriz, Ricardo Daniel
dc.contributor.author
Gutierrez, Lucas Joel
dc.date.available
2017-03-30T20:13:06Z
dc.date.issued
2015-03
dc.identifier.citation
Vega Hissi, Esteban Gabriel; Tosso, Rodrigo David; Enriz, Ricardo Daniel; Gutierrez, Lucas Joel; Molecular Insight into the Interaction Mechanisms of Amino-2H-Imidazole Derivatives With BACE1 Protease: A QM/MM and QTAIM Study; Wiley; International Journal of Quantum Chemistry; 115; 6; 3-2015; 389-397
dc.identifier.issn
0020-7608
dc.identifier.uri
http://hdl.handle.net/11336/14560
dc.description.abstract
In this study, we described quantitatively the interactions between two new amino-2H-imidazole inhibitors ((R)-1t and (S)-1m) and BACE1 using a hybrid quantum mechanics-molecular mechanical (QM/MM) method together with a quantum theory of atoms In Molecules (QTAIM) analysis. Our computational calculations revealed that the binding affinity of these compounds is mostly related to the amino-2H-imidazole core, which interact tightly with the aspartate dyad of the active site. The interactions were stronger when the inhibitors presented a bulky substituent with a hydrogen bond acceptor motif pointing toward Trp76, such as the 3,5-dimethyl-4-methoxyphenyl group of compound (S)-1m. Furthermore, the QTAIM analysis revealed that many hydrophobic interactions complement cooperatively the hydrogen bond which is not present when compound (R)-1t is bound to the enzyme. The combined QM/MM-QTAIM analysis allows identifying the interactions that account for the activity difference between compounds, even at a nanomolar range.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Wiley
dc.rights
info:eu-repo/semantics/restrictedAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Alzheimer
dc.subject
Qtaim
dc.subject
Inhibitor
dc.subject
Modeling
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Físico-Química, Ciencia de los Polímeros, Electroquímica
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Ciencias Químicas
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CIENCIAS NATURALES Y EXACTAS
dc.title
Molecular Insight into the Interaction Mechanisms of Amino-2H-Imidazole Derivatives With BACE1 Protease: A QM/MM and QTAIM Study
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2017-03-30T18:24:39Z
dc.identifier.eissn
1097-461X
dc.journal.volume
115
dc.journal.number
6
dc.journal.pagination
389-397
dc.journal.pais
Estados Unidos
dc.journal.ciudad
Hoboken
dc.description.fil
Fil: Vega Hissi, Esteban Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina. Universidad Nacional de San Luis. Facultad de Quimica, Bioquimica y Farmacia. Departamento de Quimica; Argentina
dc.description.fil
Fil: Tosso, Rodrigo David. Universidad Nacional de San Luis. Facultad de Quimica, Bioquimica y Farmacia. Departamento de Quimica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
dc.description.fil
Fil: Enriz, Ricardo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina. Universidad Nacional de San Luis. Facultad de Quimica, Bioquimica y Farmacia. Departamento de Quimica; Argentina
dc.description.fil
Fil: Gutierrez, Lucas Joel. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas y Naturales y Agrimensura. Departamento de Química. Laboratorio de Estructura Molecular y Propiedades; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.journal.title
International Journal of Quantum Chemistry
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1002/qua.24854/abstract
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1002/qua.24854


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