Biological Implications of the Intrinsic Deformability of Human Acetylcholinesterase Induced by Diverse Compounds: A Computational Study
The enzyme acetylcholinesterase (AChE) plays a crucial role in the termination of nerve impulses by hydrolyzing the neurotransmitter acetylcholine (ACh). The inhibition of AChE has emerged as a promising therapeutic approach for the management of neurological disorders such as Lewy body dementia and...
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2024-12-01
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| author | Ysaías J. Alvarado Lenin González-Paz José L. Paz Marcos A. Loroño-González Julio Santiago Contreras Carla Lossada Alejandro Vivas Yovani Marrero-Ponce Felix Martinez-Rios Patricia Rodriguez-Lugo Yanpiero Balladores Joan Vera-Villalobos |
| author_facet | Ysaías J. Alvarado Lenin González-Paz José L. Paz Marcos A. Loroño-González Julio Santiago Contreras Carla Lossada Alejandro Vivas Yovani Marrero-Ponce Felix Martinez-Rios Patricia Rodriguez-Lugo Yanpiero Balladores Joan Vera-Villalobos |
| author_sort | Ysaías J. Alvarado |
| collection | DOAJ |
| description | The enzyme acetylcholinesterase (AChE) plays a crucial role in the termination of nerve impulses by hydrolyzing the neurotransmitter acetylcholine (ACh). The inhibition of AChE has emerged as a promising therapeutic approach for the management of neurological disorders such as Lewy body dementia and Alzheimer’s disease. The potential of various compounds as AChE inhibitors was investigated. In this study, we evaluated the impact of natural compounds of interest on the intrinsic deformability of human AChE using computational biophysical analysis. Our approach incorporates classical dynamics, elastic networks (ENM and NMA), statistical potentials (CUPSAT and SWOTein), energy frustration (Frustratometer), and volumetric cavity analyses (MOLE and PockDrug). The results revealed that cyanidin induced significant changes in the flexibility and rigidity of AChE, especially in the distribution and volume of internal cavities, compared to model inhibitors such as TZ2PA6, and through a distinct biophysical-molecular mechanism from the other inhibitors considered. These findings suggest that cyanidin could offer potential mechanistic pathways for future research and applications in the development of new treatments for neurodegenerative diseases. |
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| institution | Kabale University |
| issn | 2079-7737 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biology |
| spelling | doaj-art-04495e887a2d4d70842b5913a8f53b722024-12-27T14:12:11ZengMDPI AGBiology2079-77372024-12-011312106510.3390/biology13121065Biological Implications of the Intrinsic Deformability of Human Acetylcholinesterase Induced by Diverse Compounds: A Computational StudyYsaías J. Alvarado0Lenin González-Paz1José L. Paz2Marcos A. Loroño-González3Julio Santiago Contreras4Carla Lossada5Alejandro Vivas6Yovani Marrero-Ponce7Felix Martinez-Rios8Patricia Rodriguez-Lugo9Yanpiero Balladores10Joan Vera-Villalobos11Laboratorio de Química Biofísica Experimental y Teórica (LQBET), Instituto Venezolano de Investigaciones Científicas (IVIC), Centro de Biomedicina Molecular (CBM), Maracaibo 4001, Zulia, República Bolivariana de VenezuelaLaboratorio de Modelado, Dinamica y Bioquímica Subcelular (LMDBS), Instituto Venezolano de Investigaciones Científicas (IVIC), Centro de Biomedicina Molecular (CBM), Maracaibo 4001, Zulia, República Bolivariana de VenezuelaDepartamento Académico de Química Inorgánica, Facultad de Química e Ingeniería Química, Universidad Nacional Mayor de San Marcos, Lima 15081, PeruDepartamento Académico de Fisicoquímica, Facultad de Química e Ingeniería Química, Universidad Nacional Mayor de San Marcos, Lima 15081, PeruDepartamento Académico de Química Orgánica, Facultad de Química e Ingeniería Química, Universidad Nacional Mayor de San Marcos, Lima 15081, PeruLaboratorio de Modelado, Dinamica y Bioquímica Subcelular (LMDBS), Instituto Venezolano de Investigaciones Científicas (IVIC), Centro de Biomedicina Molecular (CBM), Maracaibo 4001, Zulia, República Bolivariana de VenezuelaLaboratorio de Modelado, Dinamica y Bioquímica Subcelular (LMDBS), Instituto Venezolano de Investigaciones Científicas (IVIC), Centro de Biomedicina Molecular (CBM), Maracaibo 4001, Zulia, República Bolivariana de VenezuelaFacultad de Ingeniería, Universidad Panamericana, Augusto Rodin 498, Insurgentes Mixcoac, Benito Juárez, Ciudad de México 03920, MéxicoFacultad de Ingeniería, Universidad Panamericana, Augusto Rodin 498, Insurgentes Mixcoac, Benito Juárez, Ciudad de México 03920, MéxicoLaboratorio de Química Biofísica Experimental y Teórica (LQBET), Instituto Venezolano de Investigaciones Científicas (IVIC), Centro de Biomedicina Molecular (CBM), Maracaibo 4001, Zulia, República Bolivariana de VenezuelaLaboratorio de Física de la Materia Condensada, Instituto Venezolano de Investigaciones Científicas (IVIC), Apartado 20632, Caracas, República Bolivariana de VenezuelaLaboratorio de Análisis Químico Instrumental (LAQUINS), Facultad de Ciencias Naturales y Matemáticas, Departamento de Química y Ciencias Ambientales, Escuela Superior Politécnica del Litoral, Guayaquil ECO90211, EcuadorThe enzyme acetylcholinesterase (AChE) plays a crucial role in the termination of nerve impulses by hydrolyzing the neurotransmitter acetylcholine (ACh). The inhibition of AChE has emerged as a promising therapeutic approach for the management of neurological disorders such as Lewy body dementia and Alzheimer’s disease. The potential of various compounds as AChE inhibitors was investigated. In this study, we evaluated the impact of natural compounds of interest on the intrinsic deformability of human AChE using computational biophysical analysis. Our approach incorporates classical dynamics, elastic networks (ENM and NMA), statistical potentials (CUPSAT and SWOTein), energy frustration (Frustratometer), and volumetric cavity analyses (MOLE and PockDrug). The results revealed that cyanidin induced significant changes in the flexibility and rigidity of AChE, especially in the distribution and volume of internal cavities, compared to model inhibitors such as TZ2PA6, and through a distinct biophysical-molecular mechanism from the other inhibitors considered. These findings suggest that cyanidin could offer potential mechanistic pathways for future research and applications in the development of new treatments for neurodegenerative diseases.https://www.mdpi.com/2079-7737/13/12/1065Alzheimer’s diseasestructural flexibilityAChE inhibitors |
| spellingShingle | Ysaías J. Alvarado Lenin González-Paz José L. Paz Marcos A. Loroño-González Julio Santiago Contreras Carla Lossada Alejandro Vivas Yovani Marrero-Ponce Felix Martinez-Rios Patricia Rodriguez-Lugo Yanpiero Balladores Joan Vera-Villalobos Biological Implications of the Intrinsic Deformability of Human Acetylcholinesterase Induced by Diverse Compounds: A Computational Study Biology Alzheimer’s disease structural flexibility AChE inhibitors |
| title | Biological Implications of the Intrinsic Deformability of Human Acetylcholinesterase Induced by Diverse Compounds: A Computational Study |
| title_full | Biological Implications of the Intrinsic Deformability of Human Acetylcholinesterase Induced by Diverse Compounds: A Computational Study |
| title_fullStr | Biological Implications of the Intrinsic Deformability of Human Acetylcholinesterase Induced by Diverse Compounds: A Computational Study |
| title_full_unstemmed | Biological Implications of the Intrinsic Deformability of Human Acetylcholinesterase Induced by Diverse Compounds: A Computational Study |
| title_short | Biological Implications of the Intrinsic Deformability of Human Acetylcholinesterase Induced by Diverse Compounds: A Computational Study |
| title_sort | biological implications of the intrinsic deformability of human acetylcholinesterase induced by diverse compounds a computational study |
| topic | Alzheimer’s disease structural flexibility AChE inhibitors |
| url | https://www.mdpi.com/2079-7737/13/12/1065 |
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