Figure 7.

Comparative analysis of structural models of TNF surface potentials at pH 7.4 (A) or pH 6.0 (B) and analysis of the positioning of residues that were substituted with His in the adalimumab Fab structure (C-E). The electropotential of trimeric TNF at pH 7.4 (A) or pH 6.0 (B) is shown by blue (positive charge density) and red (negative charge density) surface coloring and opposing heavy and light chains are depicted as cartoons. Gray surface coloring indicates neutral/hydrophobic regions. Detailed view of adalimumab Fab–TNF binding interface with TNF surface potential at pH 6.0 (C-E). Side-chains of residues that were replaced with histidines within adalimumab light chain CDRs (green) or heavy chain CDRs (yellow) are shown as balls and sticks (magenta in LC, red in HC) for (C) PSV#1, (D) PSV#2 and (E) PSV#3. The model was generated with published X-ray structures (PDB 1TNF and 3WD5) using YASARA structure and POVRay and the electropotential was displayed with 60 kJ/mol. Within the light chain, Asp-1 and Ile-2 residues were not displayed to allow better insights into the binding interface.