Dynamics Determine Signaling in a Multicomponent System Associated with Rheumatoid Arthritis

摘要: Strategies that target multiple components are usually required for treatment of diseases originating from complex biological systems. The multicomponent system consisting the DR4 major histocompatibility type II molecule, glycopeptide CII259–273 collagen, and a T-cell receptor is associated with development rheumatoid arthritis (RA). We introduced non-native amino acids amide bond isosteres into investigated effect on binding to subsequent response. Molecular dynamics simulations revealed complexes between derivatives were highly dynamic. Signaling in overall was found depend formation an appropriate number dynamic intramolecular hydrogen bonds CII259–273, together positioning galactose moiety groove. Interestingly, tolerated modifications at several positions indicating opportun...