title: Computational approach for the assessment of inhibitory potency against beta-amyloid aggregation.
abstract: Beta-amyloid (Aβ) plaques are one of the hallmarks of Alzheimer's disease. Their presence in the brain leads to neurodegeneration and memory decline. Therefore, search for new drugs able to decrease formation of such deposits is of great interest. Our previously developed multifunctional compounds inhibited transformation of monomers into fibrils. Herein, we describe the computational approach for the assessment of inhibitory activity against Aβ aggregation. The influence of novel inhibitors on amyloid Aβ17-42was studied by employing of molecular docking and all-atom molecular dynamics simulations. We found that the number of intermolecular backbone hydrogen bonds at the end of 100ns MD simulation was correlated with the level of anti-aggregation potency of studied compounds. Such data may be successfully applied to in silico design of novel inhibitors of Aβ aggregation.
authors.affiliation: Department of Physicochemical Drug Analysis, Faculty of Pharmacy, Jagiellonian University Medical College, 30-688 Cracow, Medyczna 9, Poland; Faculty of Chemistry, University of Warsaw, 02-093 Warsaw, Pasteura 1, Poland. Electronic address: marek.bajda@uj.edu.pl.
authors.forename: Marek
authors.initials: M
authors.lastname: Bajda
authors.affiliation: Faculty of Chemistry, University of Warsaw, 02-093 Warsaw, Pasteura 1, Poland.
authors.forename: Sławomir
authors.initials: S
authors.lastname: Filipek
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry*; D003474:Curcumin / Q000737:chemistry; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D008024:Ligands; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D010446:Peptide Fragments / Q000737:chemistry*; D010797:Phthalimides / Q000737:chemistry*; D055503:Protein Multimerization
chemical_list: D016229:Amyloid beta-Peptides; D008024:Ligands; D010446:Peptide Fragments; D010797:Phthalimides; C086839:amyloid beta-protein (17-42); D003474:Curcumin
keywords: Aggregation; Beta-amyloid; Inhibitors; Molecular dynamics; Simulations