title: Balancing Inflammation: Computational Design of Small-Molecule Toll-like Receptor Modulators.
abstract: As essential proteins of the innate immune system, Toll-like receptors (TLRs) are involved in a plethora of physiological pathologies and their modulation is an ongoing quest in the field of drug discovery. Although TLRs recognize an unusually broad range of different molecular patterns, only a few small-molecule TLR modulators have been reported to date. Recent advances in crystallography and in silico techniques provide promising opportunities for TLR investigations and drug design. Here, three application areas for computational approaches are considered: (i) exploration of TLR structure and activation; (ii) understanding TLR modulation; and (iii) TLR drug discovery. By providing an overview on state-of-the-art computational methods, we highlight the value of molecular modeling in mechanistically understanding TLR function and guiding drug design.
authors.affiliation: Computer-Aided Drug Design, Institute of Pharmacy, Freie Universität Berlin, Königin-Luise Strasse 2+4, 14195 Berlin, Germany.
authors.forename: Manuela S
authors.initials: MS
authors.lastname: Murgueitio
authors.affiliation: Computer-Aided Drug Design, Institute of Pharmacy, Freie Universität Berlin, Königin-Luise Strasse 2+4, 14195 Berlin, Germany.
authors.forename: Christin
authors.initials: C
authors.lastname: Rakers
authors.affiliation: Computer-Aided Drug Design, Institute of Pharmacy, Freie Universität Berlin, Königin-Luise Strasse 2+4, 14195 Berlin, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Frank
authors.affiliation: Computer-Aided Drug Design, Institute of Pharmacy, Freie Universität Berlin, Königin-Luise Strasse 2+4, 14195 Berlin, Germany. Electronic address: gerhard.wolber@fu-berlin.de.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Wolber
mesh_terms: D000818:Animals; D015195:Drug Design; D055808:Drug Discovery; D006801:Humans; D007249:Inflammation / Q000188:drug therapy*; D051379:Mice; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D021281:Quantitative Structure-Activity Relationship; D051193:Toll-Like Receptors / Q000737:chemistry / Q000187:drug effects* / Q000502:physiology
chemical_list: D051193:Toll-Like Receptors
keywords: Toll-like receptor; drug design; inflammation; virtual screening