## 3 Results and Discussion
### MM/PBSA Binding Free Energy Calculation: Screening  
The binding free energies of the 15 complexes were then calculated with the MM/PBSA method for compound prioritization and re-ranking. For the binding free energy, MM/PBSA was used because they are widely applied due to their computational efficiency [60,78]. In this method, the final state of the system is sampled, and the solvent is implicitly treated to reduce computation time. In total, 80 snapshots were collected for each system at 1-ns intervals along with the last 80-ns trajectory. The average binding energy with standard deviation was calculated as well. The binding free energies for these compounds are shown in Table 3. The ranking of the compounds was performed based on the predicted binding free energy. Notably, the compound ZINC82121447 exhibited the lowest value of \(-114.03\)\(\pm\) 3.10.8 kJ/mol. \begin{table}
\begin{tabular}{c c c c c c c} \hline \hline
**PDB ID** & \(\Delta E_{\text{vdW}}\) & \(\Delta E_{\text{elec}}\) & \(\Delta G_{\text{pb}}\) & \(\Delta G_{\text{ap}}\) & \(\Delta G_{\text{bind}}\) & \(\text{IC}_{50}\) \\ \hline
6T10 & \(-100.6\) (0.6) & \(-56.3\) (1.9) & \(121.5\) (2.0) & \(-12.1\) (0.1) & \(-47.4\) (1.5) & 348 \\
6T11 & \(-103.6\) (0.7) & \(-84.4\) (1.8) & \(149.7\) (1.6) & \(-11.1\) (0.0) & \(-49.4\) (1.3) & 402 \\
6T12 & \(-116.6\) (0.6) & \(-67.6\) (1.6) & \(137.7\) (1.9) & \(-12.6\) (0.1) & \(-59.2\) (1.3) & 825 \\
6T01 & \(-121.9\) (0.7) & \(-62.0\) (1.7) & \(123.6\) (1.3) & \(-12.2\) (0.0) & \(-72.4\) (1.3) & 2057 \\
6T06 & \(0.0\) (0.0) & \(-0.1\) (0.0) & \(-9.8\) (4.8) & \(0.0\) (0.2) & \(-9.9\) (5.0) & 2010 \\
6T0A & \(-22.0\) (2.5) & \(-12.9\) (1.9) & \(28.2\) (3.6) & \(-2.8\) (0.3) & \(-9.5\) (2.8) & 2040 \\
6T0C & \(-101.3\) (0.6) & \(-49.9\) (1.9) & \(132.1\) (1.7) & \(-10.8\) (0.0) & \(-30.0\) (1.4) & 155 \\
6T0D & \(-109.7\) (0.8) & \(-72.0\) (1.4) & \(133.4\) (1.4) & \(-11.7\) (0.1) & \(-60.1\) (1.4) & 391 \\
6 SZT & \(-1.3\) (0.5) & \(-0.8\) (0.5) & \(1.1\) (2.6) & \(-0.3\) (0.1) & \(-1.2\) (2.5) & 1615 \\
6 SZT & \(-134.4\) (0.7) & \(-56.5\) (2.6) & \(141.1\) (2.4) & \(-12.8\) (0.0) & \(-62.5\) (1.4) & 1926 \\
6 SZX & \(-149.4\) (1.0) & \(-56.8\) (1.8) & \(146.5\) (1.9) & \(-14.3\) (0.1) & \(-74.1\) (1.2) & 228 \\ \hline \hline \end{tabular}
\end{table} 
Table 2: MM/PBSA-based binding free energies (in kJ/mol) with various energy components. Standard errors of the means are shown in parentheses. IC\({}_{50}\) is in the unit of \(\mu\)M.  
Other compounds, ZINC02170552, ZINC65274016, ZINC10763862, and ZINC02412146, also showed highly favorable values of \(-\)83.2656 \(\pm\) 20.4, \(-\)75.24 \(\pm\) 8.4, \(-\)73.359 \(\pm\) 8.4, and \(-\)67.716 \(\pm\) 9.4 kJ/mol, respectively. Five compounds (Table 4) were selected as potential hits based on the docking score, visual inspection, protein-ligand interactions, stability of the bound ligand, and predicted values for binding free energy. Van der Waals interactions contributed primarily to their favorable binding. Electrostatic interaction contributed less, except in the case of the first compound. This shows that van der Waals interactions played an essential role between the ligand and the protein in this study. Moreover, MM/PBSA analysis for 15 compounds is listed in Table S3. Figure 5: Correlation between experimental IC\({}_{50}\) values and \(\Delta\)G\({}_{\text{MM/PBSA}}\). \(r\) and \(\rho\) represent the Pearson correlation coefficient and Spearman’s rank correlation coefficient, respectively.