title: Structure Based Modeling of Small Molecules Binding to the TLR7 by Atomistic Level Simulations.
abstract: Toll-Like Receptors (TLR) are a large family of proteins involved in the immune system response. Both the activation and the inhibition of these receptors can have positive effects on several diseases, including viral pathologies and cancer, therefore prompting the development of new compounds. In order to provide new indications for the design of Toll-Like Receptor 7 (TLR7)-targeting drugs, the mechanism of interaction between the TLR7 and two important classes of agonists (imidazoquinoline and adenine derivatives) was investigated through docking and Molecular Dynamics simulations. To perform the computational analysis, a new model for the dimeric form of the receptors was necessary and therefore created. Qualitative and quantitative differences between agonists and inactive compounds were determined. The in silico results were compared with previous experimental observations and employed to define the ligand binding mechanism of TLR7.
authors.affiliation: Department of Physics, University of Alberta, Edmonton, AB T6G 2E1, Canada. fgentile@ualberta.ca.
authors.forename: Francesco
authors.initials: F
authors.lastname: Gentile
authors.affiliation: Institute of Computer Integrated Manufacturing for Sustainable Innovation, Department of Innovative Technologies, University of Applied Sciences and Arts of Southern Switzerland (SUPSI), Manno CH-6928, Switzerland. marco.deriu@supsi.ch.
authors.forename: Marco A
authors.initials: MA
authors.lastname: Deriu
authors.affiliation: Institute of Computer Integrated Manufacturing for Sustainable Innovation, Department of Innovative Technologies, University of Applied Sciences and Arts of Southern Switzerland (SUPSI), Manno CH-6928, Switzerland. ginevra.licandro@icimsi.ch.
authors.forename: Ginevra
authors.initials: G
authors.lastname: Licandro
authors.affiliation: Institute of Computer Integrated Manufacturing for Sustainable Innovation, Department of Innovative Technologies, University of Applied Sciences and Arts of Southern Switzerland (SUPSI), Manno CH-6928, Switzerland. alessio.prunotto@supsi.ch.
authors.forename: Alessio
authors.initials: A
authors.lastname: Prunotto
authors.affiliation: Institute of Computer Integrated Manufacturing for Sustainable Innovation, Department of Innovative Technologies, University of Applied Sciences and Arts of Southern Switzerland (SUPSI), Manno CH-6928, Switzerland. andrea.danani@supsi.ch.
authors.forename: Andrea
authors.initials: A
authors.lastname: Danani
authors.affiliation: Department of Physics, University of Alberta, Edmonton, AB T6G 2E1, Canada. jackt@ualberta.ca.|Cross Cancer Institute, Department of Oncology, University of Alberta, Edmonton, AB T6G 1Z2, Canada. jackt@ualberta.ca.
authors.forename: Jack A
authors.initials: JA
authors.lastname: Tuszynski
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology; D000225:Adenine / Q000031:analogs & derivatives / Q000737:chemistry*; D019295:Computational Biology / Q000379:methods*; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D011485:Protein Binding / Q000502:physiology; D017434:Protein Structure, Tertiary; D011804:Quinolines / Q000737:chemistry*; D051199:Toll-Like Receptor 7 / Q000737:chemistry* / Q000378:metabolism*; D051200:Toll-Like Receptor 8 / Q000737:chemistry
chemical_list: D011804:Quinolines; C495348:TLR7 protein, human; C495349:TLR8 protein, human; D051199:Toll-Like Receptor 7; D051200:Toll-Like Receptor 8; C037219:quinoline; D000225:Adenine
keywords: adenine derivatives; homology modeling; imidazoquinoline; immune system; molecular docking; molecular dynamics; toll-like receptors