Table 1.
Calculated docking scores (kcal·mol−1) from molecular docking of various PET probes in the different binding sites of TauPiD protofibril. Values in brackets are the binding energies from the rescoring function X-Score for the same binding pose. Site C1 corresponds to a cavity site while the remainder (S1 to S11) correspond to surface binding sites. Corresponding binding sites are shown in Figure 1B.
| Binding Site |
AV-1451 | MK-6240 | PBB3 | PM-PBB3 | THK5351 | PiB |
|---|---|---|---|---|---|---|
| C1 | −11.0 (−8.9) | −11.0 (−9.0) | −10.1 (−9.4) | −10.0 (−9.4) | −10.3 (−9.0) | −8.9 (−8.5) |
| S1 | NB | NB | −4.9 (−7.0) | NB | NB | −4.4 (−6.6) |
| S2 | −6.0 (−7.3) | NB | NB | −5.0 (−7.2) | −5.7 (−7.0) | −4.4 (−6.9) |
| S3 | NB | NB | −5.7 (−7.6) | −5.4 (−7.4) | NB | −4.6 (−7.2) |
| S4 | NB | −5.1 (−6.7) | −5.0 (−6.9) | NB | NB | −4.5 (−6.5) |
| S5 | −6.5 (−7.4) | −5.5 (−6.7) | −6.0 (−7.7) | NB | −5.8 (−7.1) | −5.2 (−7.2) |
| S6 | −8.3 (−7.9) | −7.4 (−7.7) | −7.3 (−8.0) | NB | −7.3 (−7.8) | −6.3 (−7.5) |
| S7 | −9.4 (−8.4) | NB | −8.4 (−8.7) | NB | −8.3 (−8.3) | −7.1 (−7.8) |
| S8 | −7.1 (−7.5) | NB | −6.2 (−7.6) | −6.1 (−7.5) | NB | NB |
| S9 | −5.9 (−6.7) | −5.7 (−6.9) | NB | −4.5 (−6.5) | −5.6 (−6.7) | −4.6 (−6.6) |
| S10 | −6.0 (−7.1) | NB | NB | −4.6 (−6.6) | −5.2 (−6.8) | −4.6 (−6.7) |
| S11 | NB | NB | NB | −4.5 (−6.9) | NB | −4.5 (−6.9) |
PM-PBB3 also binds to a site in the left neighbor of site S2 (S2n) with a docking score of −4.6 (−6.7) and a site in the right neighbor of site S3 (S3n) with a docking score of −3.7 (−6.8). NB; did not bind. Lowest scores among all the surface binding sites are in bold.