Balancing Inflammation: Computational Design of Small-Molecule Toll-like Receptor Modulators

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• 作者：Manuela S. Murgueitio¹ ; Christin Rakers¹ ; Anne Frank¹ ; Gerhard Wolber¹ ; ^{gerhard.wolber@fu-berlin.de}
• 关键词：Toll-like receptor ; virtual screening ; drug design ; inflammation
• 刊名：Trends in Pharmacological Sciences
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：38
• 期：2
• 页码：155-168
• 全文大小：2710 K
• 卷排序：38

文摘

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.