caa a22 4500 605513716 CHVBK 20210128100701.0 cr unu---uuuuu 210128e20151101xx s 000 0 eng 10.1007/s00894-015-2835-6 doi (NATIONALLICENCE)springer-10.1007/s00894-015-2835-6 Molecular modeling studies demonstrate key mutations that could affect the ligand recognition by influenza AH1N1 neuraminidase [Elektronische Daten] [Gema Ramírez-Salinas, J. García-Machorro, Miguel Quiliano, Mirko Zimic, Verónica Briz, Saul Rojas-Hernández, J. Correa-Basurto] The goal of this study was to identify neuraminidase (NA) residue mutants from human influenza AH1N1 using sequences from 1918 to 2012. Multiple alignment studies of complete NA sequences (5732) were performed. Subsequently, the crystallographic structure of the 1918 influenza (PDB ID: 3BEQ-A) was used as a wild-type structure and three-dimensional (3-D) template for homology modeling of the mutated selected NA sequences. The 3-D mutated NAs were refined using molecular dynamics (MD) simulations (50ns). The refined 3-D models were used to perform docking studies using oseltamivir. Multiple sequence alignment studies showed seven representative mutations (A232V, K262R, V263I, T264V, S367L, S369N, and S369K). MD simulations applied to 3-D NAs showed that each NA had different active-site shapes according to structural surface visualization and docking results. Moreover, Cartesian principal component analyses (cPCA) show structural differences among these NA structures caused by mutations. These theoretical results suggest that the selected mutations that are located outside of the active site of NA could affect oseltamivir recognition and could be associated with resistance to oseltamivir. Springer-Verlag Berlin Heidelberg, 2015 Docking nationallicence Influenza A H1N1 nationallicence Molecular dynamics simulations nationallicence Mutations nationallicence Neuraminidase nationallicence Ramírez-Salinas Gema Laboratorio de Modelado Molecular y Bioinformática, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón, 11340, México City, Mexico aut García-Machorro J. Laboratorio de Medicina de Conservación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón, 11340, Mexico, DF, México aut Quiliano Miguel Unidad de Bioinformática y Biología Molecular, Laboratorios de Investigación y Desarrollo, Universidad Peruana Cayetano Heredia, Lima, Perú aut Zimic Mirko Unidad de Bioinformática y Biología Molecular, Laboratorios de Investigación y Desarrollo, Universidad Peruana Cayetano Heredia, Lima, Perú aut Briz Verónica Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, España aut Rojas-Hernández Saul Laboratory of Immunology, School of Medicine, National Polytechnic Institute, Mexico, DF, Mexico aut Correa-Basurto J. Laboratorio de Modelado Molecular y Bioinformática, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón, 11340, México City, Mexico aut Journal of Molecular Modeling Springer Berlin Heidelberg 21/11(2015-11-01), 1-14 1610-2940 21:11<1 2015 21 894 https://doi.org/10.1007/s00894-015-2835-6 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00894-015-2835-6 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Ramírez-Salinas Gema Laboratorio de Modelado Molecular y Bioinformática, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón, 11340, México City, Mexico aut NATIONALLICENCE 700 1- García-Machorro J. Laboratorio de Medicina de Conservación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón, 11340, Mexico, DF, México aut NATIONALLICENCE 700 1- Quiliano Miguel Unidad de Bioinformática y Biología Molecular, Laboratorios de Investigación y Desarrollo, Universidad Peruana Cayetano Heredia, Lima, Perú aut NATIONALLICENCE 700 1- Zimic Mirko Unidad de Bioinformática y Biología Molecular, Laboratorios de Investigación y Desarrollo, Universidad Peruana Cayetano Heredia, Lima, Perú aut NATIONALLICENCE 700 1- Briz Verónica Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, España aut NATIONALLICENCE 700 1- Rojas-Hernández Saul Laboratory of Immunology, School of Medicine, National Polytechnic Institute, Mexico, DF, Mexico aut NATIONALLICENCE 700 1- Correa-Basurto J. Laboratorio de Modelado Molecular y Bioinformática, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón, 11340, México City, Mexico aut NATIONALLICENCE 773 0- Journal of Molecular Modeling Springer Berlin Heidelberg 21/11(2015-11-01), 1-14 1610-2940 21:11<1 2015 21 894