Figure 5

24HC produces significant conformational changes in the specificity-determining loop (SDL) in the βI-domain of integrin αvβ3. (A) SDL undergoes extensive conformational changes during 200 ns MD simulations. The time evolution of the entire loop (residues 158–190) is shown at various time intervals from the start (red color) to the end (blue color). (B) The root-mean-square-fluctuations (RMSF) indicate the extent of conformational changes in the βI-domain observed during the simulations. In addition to SDL, both α1 and α7 helices undergo moderate fluctuations. (C–D) 24HC binding disrupts H-bond networks within the SDL residues and between SDL and the β-propeller domain. SDL is shown at the start and end of the simulation in pink and cyan colors, respectively. The H-bonds between Y122 and T182 and T182 and K125 broke after 30 ns. The H-bond between Y122 and K125 broke after around 100 ns. The H-bond between the residues P169 from SDL (βI) and Q120 from the β-propeller domain quickly moved apart from 2.9 to 16.6 Å. The β-propeller domain (with Q120) is shown at the start and end of the simulation in green and light blue colors, respectively.