Computational Approaches to Toll-Like Receptor 4 Modulation

摘要: Toll-like receptor 4 (TLR4), along with its accessory protein myeloid differentiation factor 2 (MD-2), builds a heterodimeric complex that specifically recognizes lipopolysaccharides (LPS), which are present on the cell wall of Gram-negative bacteria, activating innate immune response. Some TLR4 modulators undergoing preclinical and clinical evaluation for treatment sepsis, inflammatory diseases, cancer rheumatoid arthritis. Since relatively recent elucidation X-ray crystallographic structure extracellular domain TLR4, research around this fascinating has risen to new level, thus, perspectives have been opened. In particular, diverse computational techniques applied decipher some basis at atomic level regarding mechanism functioning ligand recognition processes involving TLR4/MD-2 system level. This review summarizes reported molecular modeling studies recently provided insights into regulating activation/inactivation key interactions modulating process by agonist antagonist ligands. These contributed design discovery novel small molecules promising activity as modulators.