New small-size peptides modulators of the exosite of BACE1 obtained from a structure-based design
| Autor: | Emilio Angelina, Lucas J. Gutierrez, Ricardo D. Enriz, Lívia Fülöp, Héctor A. Baldoni, Botond Penke, Andrea Gyebrovszki, Nelida Maria Peruchena |
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| Rok vydání: | 2016 |
| Předmět: |
Models
Molecular 0301 basic medicine Molecular model Molecular Conformation Ab initio Quantitative Structure-Activity Relationship MOLECULAR SIMULATIONS Molecular Dynamics Simulation 010402 general chemistry 01 natural sciences Molecular Docking Simulation 03 medical and health sciences Molecular dynamics Structural Biology Computational chemistry mental disorders Β-SECRETASE Aspartic Acid Endopeptidases Humans Non-covalent interactions Protein Interaction Domains and Motifs MOLECULAR MODELING Molecular Biology chemistry.chemical_classification Binding Sites ALZHEIMER’S DISEASE Otras Ciencias Químicas Atoms in molecules Ciencias Químicas General Medicine Combinatorial chemistry Small molecule 0104 chemical sciences 030104 developmental biology chemistry Drug Design Density functional theory Amyloid Precursor Protein Secretases EXOSITE-MODULATORS Peptides CIENCIAS NATURALES Y EXACTAS |
| Zdroj: | Journal of Biomolecular Structure and Dynamics. 35:413-426 |
| ISSN: | 1538-0254 0739-1102 |
| DOI: | 10.1080/07391102.2016.1145143 |
| Popis: | We report here two new small-size peptides acting as modulators of the β-site APP cleaving enzyme 1 (BACE1) exosite. Ac-YPYFDPL-NH2 and Ac-YPYDIPL-NH2 displayed a moderate but significant inhibitory effect on BACE1. These peptides were obtained from a molecular modeling study. By combining MD simulations with ab initio and DFT calculations, a simple and generally applicable procedure to evaluate the binding energies of small-size peptides interacting with the exosite of the BACE1 is reported here. The structural aspects obtained for the different complexes were analyzed providing a clear picture about the binding interactions of these peptides. These interactions have been investigated within the framework of the density functional theory and the quantum theory of atoms in molecules using a reduced model. Although the approach used here was traditionally applied to the study of noncovalent interactions in small molecules complexes in gas phase, we show, through in this work, that this methodology is also a very powerful tool for the study of biomolecular complexes, providing a very detailed description of the binding event of peptides modulators at the exosite of BACE1. Fil: Gutierrez, Lucas Joel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas y Naturales y Agrimensura. Departamento de Química. Laboratorio de Estructura Molecular y Propiedades; Argentina Fil: Angelina, Emilio Luis. 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 Fil: Gyebrovszki, Andrea. University of Szeged. Department of Medical Chemistry; Hungría Fil: Fülöp, Livia. University of Szeged. Department of Medical Chemistry; Hungría Fil: Peruchena, Nelida Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Química Básica y Aplicada del Nordeste Argentino. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Instituto de Química Básica y Aplicada del Nordeste Argentino; Argentina Fil: Baldoni, Hector Armando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Matemática Aplicada de San Luis ; Argentina Fil: Penke, Botond. University of Szeged. Department of Medical Chemistry; Hungría Fil: Enriz, Ricardo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina |
| Databáze: | OpenAIRE |
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