Table 1. Top scoring ligands identified through virtual screening.
| Ligand | Target structure | Site | Free energy (Kcal/mol) | Interactions |
|---|---|---|---|---|
| ZINC29590259 | 4LX0_C* | Site 1 | -8.9 | Hydrogen bonds-ASP19, SER20, ASN101, ARG104, GLU108, ASP111, HIS112 |
| 5C46_F* | Site 1 | -8.2 | Hydrophobic interactions- TYR99, VAL102, GLU103, ARG104, LYS107, PHE142 Hydrogen bonds-ARG74, GLU100, ARG104 Salt bridge- LYS107 |
|
| 1OIV_A* | Site 1 | -8.5 | Hydrophobic interactions- ARG74, THR77 Hydrogen bonds- SER20, ARG72 π-Cation Interaction- HIS112 |
|
| 4OJK_A* | Site 2 | -8.4 | Hydrophobic interactions-GLU103, LEU106 Hydrogen bonds-LEU148, GLU171 |
|
| ZINC29590263 | 4LX0_C* | Site 1 | -9 | Hydrogen bonds- ASP19, SER20, ARG104, GLU108, ASP111, HIS112 |
| 4OJK_A | Site 2 | -8.3 | Hydrophobic interactions- GLU103, LEU106 Hydrogen bonds- LEU148, GLU171 |
|
| ZINC18141294 | 1OIV_A* | Site 1 | -8.9 | Hydrogen bonds-SER20, ASN101, ARG104, GLU108, HIS112 |
| 4OJK_A* | Site 2 | -8 | Hydrogen bonds- ILE117, ILE119, ASN146, GLU171 | |
| ZINC01690699 | 4LX0_C* | Site 1 | -9.9 | Hydrogen bonds- ASP19, GLU108 |
| 1OIV_A | Site 1 | -8.6 | Hydrogen bonds- ASP19, SER20, GLU108, ASP111, HIS112 π-Cation Interaction- HIS112 |
|
| 4C4P_A | Site 2 | -8.6 | Hydrogen bonds-ALA113, SER115, ILE119, GLY147 π-Cation Interaction- HIS112 |
|
| 5C46_F* | Site 1 | -8.7 | Hydrogen bonds- ARG74, GLU100, ARG104 | |
| 4UJ5_B* | Site 2 | -8.9 | Hydrogen bonds-ILE117, ASN146 | |
| 1YZK_A* | Site 2 | -8.6 | Hydrogen bonds- ALA113, ILE119, GLY147 |
|
| 5JCZ_D* | Site 1 | -8.3 | Hydrogen bonds- ASP19, ASN101, GLU103, ARG104 | |
| ZINC04773602 | 1YZK_A* | Site 2 | -8 | Hydrophobic interactions- LEU106, LEU109, ARG110, VAL118, ILE119, ASN146, LEU148, GLU171, ILE175 Hydrogen bond- ILE119 |
| ZINC29590257 | 5C46_F* | Site 1 | -8.2 | Hydrophobic interactions- TYR99, VAL102, LYS107, PHE142 Hydrogen bonds- ARG74, GLU100, GLU103, ARG104 Salt bridge- LYS107 |
| 4LX0_C* | Site 1 | -8.7 | Hydrogen bonds- ASP19, ARG74, ASN101, ARG104 | |
| 4OJK_A* | Site 2 | -8.4 | Hydrophobic interactions-GLU103, LEU106 Hydrogen bonds- ASN147, SER149 |
|
| ZINC13099051 | 4LX0_C* | Site 1 | -9.4 | Hydrophobic interactions-GLU71 Hydrogen bonds- GLY69, GLU71, ARG74, GLU108 |
| 1OIV_A* | Site 1 | -8.6 | Hydrophobic interactions- LYS107, GLU108 Hydrogen bond- LYS107 |
|
| ZINC01639634 | 4LX0_C* | Site 1 | -8.6 | Hydrogen bonds- SER20, GLY69, GLU71, ARG104, GLU108 |
| ZINC18057104 | 1OIV_A* | Site 1 | -9.1 | Hydrogen bonds- ASP19, SER20, GLU108, ASP111 Salt bridge- ASP19, ASP111 |
| 4LX0_C* | Site 1 | -8.8 | Hydrogen bonds- SER20, ARG104, GLU108 Salt bridges- GLU108 |
|
| 4UJ5_B* | Site 2 | -8.3 | Hydrogen bonds- ASN146, GLU171 | |
| ZINC04783229 | 4LX0_C* | Site 1 | -9.6 | Hydrogen bonds-GLY69, ARG104, GLU108 |
| 4OJK_A* | Site 2 | -9 | Hydrogen bonds-ILE117 | |
| 4UJ5_B* | Site 1 | -8.5 | Hydrogen bonds- ASP19, ASN101 | |
| 4C4P_A | Site 2 | -8.4 | Hydrogen bonds- ILE117, GLU171 | |
| ZINC01694053 | 4LX0_C* | Site 1 | -8.6 | Hydrogen bonds- SER20, GLY69, ARG74, THR77, SER78, GLU108 |
| 4C4P_A* | Site 2 | -8.3 | Hydrogen bonds- ALA113, SER115, ILE1117, ILE119 | |
| ZINC01572309 | 1YZK_A* | Site 2 | -8.8 | Hydrogen bonds-ARG110, SER115, ASN146, GLY147 |
| 4C4P_A* | Site 2 | -8.3 | Hydrogen bonds- SER115, ASN116, GLY147, SER149, GLU171 | |
| 4OJK_A* | Site 2 | -8.4 | Hydrogen bonds- SER115, ASN116, ASN147, SER149, GLU171 | |
| 1OIV_A* | Site 1 | -8.6 | Hydrogen bonds- ASP19, ARG104, GLU108 |
|
| ZINC01707130 | 4LX0_C* | Site 1 | -8.5 | Hydrogen bonds- ASP19, SER20, GLU71 Salt bridge- ASP19 |
| ZINC01568793 | 4LX0_C* | Site 1 | -9 | Hydrophobic interactions- LEU97 Hydrogen bonds- SER20, ASN101 Salt bridges- ASP19, GLU108 |
| 5JCZ_D* | Site 1 | -8.6 | Hydrophobic interactions- THR77, GLU103 Hydrogen bonds- ARG104 π-Cation Interaction- ARG104 |
|
| 1OIV_A* | Site 1 | -8.5 | Hydrophobic interactions- LEU97 Hydrogen bonds- SER20, ARG72 π-Cation Interactions- ARG72 Salt bridges- ASP19, GLU108 |
|
| 4C4P_A* | Site 2 | -8.3 | Hydrophobic interactions- ARG110, ILE117 Salt bridge- GLU171 |
|
| 4UJ5_B* | Site 2 | -8 | Hydrophobic interactions- LYS107, VAL118 Hydrogen bonds- ILE119 |
|
| ZINC13152284 | 4LX0_C* | Site 1 | -9.2 | Hydrogen bonds- ASP19, SER20, GLY69 |
| 1OIV_A* | Site 1 | -9.1 | Hydrogen bond -104 | |
| 4UJ5_B* | Site 2 | -8.3 | Hydrogen bond- GLU171 |
Top scoring ligands, their target sites in each representative structure for which they scored best, their binding free energy values predicted by AutoDockVina, and their interactions with the respective target structures that are observed using protein-ligand interaction profiler (PLIP) are listed. Ligands are listed based on their weighted scores (see methods). The target structures for which, each ligand scored best is indicated in bold. The ligand structures are shown in Figs 4–9.
* The target structures for which the ligands are observed as hits duringredocking using Vinardo.