## 4 Conclusions
The following supporting information can be downloaded at: [[https://www.mdpi.com/article/10.3390/app14188391/s1](https://www.mdpi.com/article/10.3390/app14188391/s1)]([https://www.mdpi.com/article/10.3390/app14188391/s1](https://www.mdpi.com/article/10.3390/app14188391/s1)), Figure S1: 3D interaction plots for 15 protein-ligand complexes identified through Molecular docking process, highlighting hydrogen bonds (dashed green lines), Van der Waals interactions (light green lines), \(\pi\)-\(\pi\) stacking (magenta lines), \(\pi\)-\(\sigma\) bonding (purple lines), and other key interactions stabilizing the ligand-protein complexes; Figure S2: 2D interaction plots for 15 selected protein-ligand complexes, providing detailed insights into interactions between protein and ligands. Different colors indicate different types of bonds; Figure S3: RMSD plots of ligand and protein backbone atoms for 15 small-molecules, which are split into three plots (suffix 1-3 of plot names) for clarity. A1-A3 show the RMSDs of ligand after the protein-ligand complex being aligned according to the backbone of protein, which quantify the changes of binding poses of ligands relative to the starting poses; B1-B3 show the RMSDs of ligand after the ligand being aligned to the ligand itself, which access the conformational changes of ligands; C1-C3 show the RMSDs of protein backbone after the protein being aligned with respect to its backbone, which evaluate the conformational changes of protein backbone; Figure S4: RMSD plots of protein (black) and ligand (red) for 11 known inhibitors from an experimental study. Black lines show the RMSDs of protein (all atoms of the protein) after the protein being aligned with respect to itself, which evaluate the conformational changes of protein; Red lines show the RMSDs of ligand after the ligand being aligned to the ligand itself, which access the conformational changes of ligands. The RMSDs of some ligands (such as 6T0D, 6T06 and 6T0A) fluctuates between two values, suggesting frequent transitions between two stable conformations. Since the RMSDs are as low as 0.1-0.15, these molecules can be considered to be stable; Figure S5: Distances between the center of mass (COM) of the protein and the COM of the ligand during the 100-ns simulations for the top five compounds ranked by docking scores; Figure S6: Distances between the center of mass (COM) of the protein and the COM of the ligand during the 100-ns simulations for all the 15 compounds; Figure S7: The ligand 6 MZ is docked into active site by GeomX mode (docked pose in purple color for carbon atoms); Figure S8: Detailed molecular structures of the top-ranked ligands identified as potential YTHDC1 inhibitors; Figure S9: pKa of titratable residues predicted by H++ (orange) and DelPhiPiKa (blue) servers. The protonation states for titratable residues of ARG, LYS, GLU, ASP and HIS were thus determined to be in their default protonation state; Table S1: 1500 small-molecules, from eMolecules, sorted with docking scores using Autodock Vina; Table S2: ADMET profiling results of top 5 small-molecules. Absorption, distribution, metabolism, extinction, and toxicity parameters are highlighted with blue, light gray, green, gold, and orange colors, respectively. * Stands for ZINC; Table S3: MM/PBSA analysis of top 15 compounds are listed below; Table S4: Composition of the simulated systems for the selected 15 compounds, which includes the number of atoms of the YTHDC1 protein (receptor atoms), the number of atoms of the ligands (ligand atoms), the number of water molecule and the number of salt ions in each simulation box. **Author Contributions:** Conceptualization, W.L. and N.S. ; methodology, M.A. and N.S. ; software, M.A. and N.S; validation, M.A. and N.S; formal analysis, X.W. and W.L. ; investigation, N.S., W.L. and X.W. ; resources, W.L. ; data curation, N.S. and M.A. ; writing--original draft preparation, M.A. and N.S. ; writing--review and editing, M.A., X.W. and W.L. ; visualization, M.A. and N.S. ; supervision, W.L. ; project administration, W.L.