Table 3.
Key protein-ligand contacts of bound PpIX to the ligand binding Sites 1 and 2 inside HSA (1AO6.pdb). Computational data obtained using the CLC DDWB program [23] and BIOVIA DS Visualizer software [24].
| Hydrogen Bonding Interactions | |||||||
| Site 1 | Site 2 | ||||||
| PDB atom name | Ligand atom | Type of contact | Distance (Å) | PDB atom name | Ligand atom | Type of contact | Distance (Å) |
| (D) Arg117:HN (bb) | (A) PpIX:O(pp) | Conventional | 2.02 * | (D) Lys444:HZ1 (sc) | (A) PpIX:O (pp) | Conventional | 2.01 * |
| (D) Arg117:HE (sc) | (A) PpIX:O (pp) | Conventional | 2.77 * | (D) Lys444:HZ1 (sc) | (A) PpIX:O (pp) | Conventional | 2.25 * |
| (D) Tyr161:HH (sc) | (A) PpIX:O (pp) | Conventional | 2.00 * | (D) Lys444:HZ2 (sc) | (A) PpIX:O (pp) | Conventional | 2.58 * |
| (D) Arg186:HE (sc) | (A) PpIX: (r) | π-Donor Non classical | 3.01 * | (D) PpIX:NH (r) (A) PpIX:N (r) | Conventional Intramolecular | 2.21 * | |
| (D) PpIX:NH (r) (A) PpIX:N (r) | Conventional Intramolecular | 2.21 * | (D) PpIX:NH (r) (A) PpIX:N (r) | Conventional Intramolecular | 2.24 * | ||
| (D) PpIX:NH (r) (A) PpIX:N (r) | Conventional Intramolecular | 2.24 * | |||||
| Hydrophobic Interactions | |||||||
| Site 1 | Site 2 | ||||||
| PDB atom name | Ligand atom | Type of contact | Distance (Å) | PDB atom name | Ligand atom | Type of contact | Distance (Å) |
| Tyr138 (sc) | PpIX:C(v) | π-Alkyl | 5.05 | Ala191 (sc) | PpIX:C (v) | Alkyl | 4.09 |
| Ile142 (sc) | PpIX:C (m) | Alkyl | 4.52 | Ala191 (sc) | PpIX:C (m) | Alkyl | 4.10 |
| Ile142 (sc) | PpIX:C (v) | Alkyl | 4.57 | Ala194 (sc) | PpIX:C (v) | Alkyl | 3.90 |
| Ile142:CD1 (sc) | PpIX (pr) | π-σ | 3.15 | Lys195 (sc) | PpIX:C (v) | Alkyl | 4.00 |
| His146 (sc) | PpIX:C( m) | π-σ | 3.62 | Lys195 (sc) | PpIX (pr) | π-Alkyl | 4.88 |
| His146 (sc) | PpIX:C (v) | π-Alkyl | 5.10 | Leu198 (sc) | PpIX:C (m) | Alkyl | 5.14 |
| Phe149 (sc) | PpIX:C (m) | π-Alkyl | 4.83 | Trp214 (sc) | PpIX:C (v) | π-Alkyl | 4.49 |
| Phe157 (sc) | PpIX:C (v) | π-Alkyl | 4.50 | Trp214 (sc) | PpIX:C (v) | π-Alkyl | 4.61 |
| Arg186 (sc) | PpIX (chms) | π-Alkyl | 3.11 | Arg218 (sc) | PpIX:C (v) | Alkyl | 4.55 |
| Arg186 (sc) | PpIX (pr) | π-Alkyl | 3.46 | Val343 (sc) | PpIX:C (v) | Alkyl | 3.49 |
| Arg186 (sc) | PpIX (pr) | π-Alkyl | 4.35 | Lys436 (sc) | PpIX:C (m) | Alkyl | 5.31 |
| Arg186 (sc) | PpIX (pr) | π-Alkyl | 4.72 | Lys436 (sc) | PpIX:C (m) | Alkyl | 3.79 |
| Arg186 (sc) | PpIX (pr) | π-Alkyl | 5.42 | Lys436 (sc) | PpIX (pr) | π-Alkyl | 5.27 |
| Pro447 (sc) | PpIX (pr) | π-Alkyl | 5.21 | ||||
| Lys190 (sc) | PpIX:C (v) | Alkyl | 4.43 | Pro447:C,O (bb) Cys448:N (bb) | PpIX (pr) | Amide π-Stacked | 3.94 |
| Lys190 (sc) | PpIX:C (m) | Alkyl | 4.72 | Cys448 (sc) | PpIX (pr) | π-Alkyl | 5.32 |
| Lys190:CD1 (sc) | PpIX (pr) | π-σ | 3.94 | Cys448 (sc) | PpIX (chms) | π-Alkyl | 5.33 |
| Lys190 (sc) | PpIX (pr) | π-Alkyl | 5.27 | Asp451:C,O (bb) Tyr452:N (bb) | PpIX (pr) | Amide π-Stacked | 4.47 |
| Asp451:C,O (bb) Tyr452:N (bb) | PpIX (chms) | Amide π-Stacked | 5.66 | ||||
| Tyr452 (sc) | PpIX (pr) | π-π T-shaped | 4.96 | ||||
| Tyr452 (sc) | PpIX (m) | π-Alkyl | 4.59 | ||||
| Tyr452 (sc) | PpIX (v) | π-Alkyl | 5.48 | ||||
| Val455 (sc) | PpIX:C (m) | Alkyl | 4.56 | ||||
| Val455 (sc) | PpIX:C (v) | Alkyl | 3.97 | ||||
| Val455 (sc) | PpIX (pr) | π-Alkyl | 5.43 | ||||
| Miscellaneous Interactions | Unfavorable Interactions | ||||||
| Site 2 | Site 2 | ||||||
| PDB atom name | Ligand atom | Type of contact | Distance (Å) | PDB atom name | Ligand atom | Type of contact | Distance (Å) |
| Cys448:SG (sc) | PpIX (pr) | π-Sulfur | 3.76 | Lys436:HZ2 (sc) | PpIX:C (m) | Steric Bumps | 1.04 |
| Lys436:HZ3 (sc) | PpIX:H (m) | Steric Bumps | 1.34 | ||||
| Lys436:NZ (sc) | PpIX:H (m) | Steric Bumps | 1.37 | ||||
| Lys436:HZ2 (sc) | PpIX:C (m) | Steric Bumps | 1.64 | ||||
| Lys436:NZ (sc) | PpIX:C (m) | Steric Bumps | 2.20 | ||||
* Strong H-bond (max distance = 3.4 Å), weak H-bond (max distance = 3.8 Å); (A), H-bond acceptor; (D), H-bond donor; (sc), side chain functional group of the amino acid; (bb), backbone; (pp), propionic acid group; (v), vinyl group; (m), methyl group; (pr), pyrrole ring; (chms), conjugated heterocyclic macrocycle system.