## 3 Results
### Target-Based Virtual Screening and Molecular Docking  
Target-based virtual screening (TBVS) is widely used to identify potential drug candidates by focusing on interactions with specific molecular targets. In our study, we selected compounds that met [PERSON]'s drug-likeness criteria [17] and aligned with the pharmacophore model designed for targeting the HSP90 protein. These selected compounds were further analyzed through molecular docking experiments to evaluate their interactions and binding affinity with HSP90. The docking results revealed binding patterns, energy scores, and potential interactions between the compounds and the HSP90 protein. Our research involves redocking the reference ligand MEY to test our molecular docking technique's accuracy and reliability. Figure 2 shows that our enzyme active site determination was accurate RMSD: 1.553. HSP90's binding pocket had two components: a hydrophobic component with Ala55, Ile96, Met98, Leu107, Phe138, and Val150, and a hydrophilic component with Asn51, Asp93, and Thr184. These findings support previous research [25]. To improve the accuracy and efficiency of our screening process, we first employed the standard precision (SP) docking approach, which is fast and allows selecting compounds capable of forming stable complexes. Subsequently, the compounds, identified by SP, were subjected to a more precise docking analysis using the extra precision (XP) approach [26]. The strength of the binding between the chemical compounds and the protein target is shown by the results obtained during the docking process. Lower scores indicate higher binding strength between the chemical and the protein; the interactions in the docking process can be better understood by analyzing and interpreting these results. Figure 1: Pharmacophore model ADDRR: acceptor (red), donor (blue), and ring (orange) representation. Five compounds (L1, L2, L3, L4, and L5) displayed docking scores lower than the reference ligand MEY (\(-\)7.94 kcal/mol), indicating strong binding affinities (Table 1). This suggests that these compounds bind more effectively and stably to the N-terminal ATP-binding region of HSP90. A visual analysis of the complex interactions, as shown in Figure 3, allowed us to further examine the doc king data. For an overview, Table S2 summarizes the types of interactions observed. Hydrogen bonds, which are known for their electrostatic strength and ability to stabilize ligand-receptor complexes, were essential in our compounds' binding to HSP90, specifically involving residues Gly97, Thr184, Asn51, and Asp93 [27; 28; 29]. Notably, these same residues were observed in the binding of the reference ligand MEY, indicating a shared interaction pattern and consistent binding mode that support the reliability of our docking results. Both hydrophobic interactions and hydrogen bonding were present between our compounds and HSP90, specifically with residues Met98, Ala55, Asp54, and Phe138, consistent with prior findings [18; 22]. Particularly, Met98 forms a pi-sulfur interaction with our compounds; in this noncovalent interaction, the pi-electron system of the aromatic rings aligns with the sulfur atom in methionine, which enhances ligand-protein affinity. Multiple interactions with the protein improve the stability of our compounds within the active site, suggesting their strong potential as HSP90 inhibitors. A summary of the compounds' properties is provided in Table S3. The pharmacokinetics and drug-likeness profiles of these candidates will be discussed in the following section. \begin{table}
\begin{tabular}{c c c c} \hline \hline
**Compound** & **CID** & **SP (kcal/mol)** & **XP (kcal/mol)** \\ \hline L1 & CID69438556 & \(-\)7.910 & \(-\)9.795 \\ \hline L2 & CID69441313 & \(-\)9.373 & \(-\)9.636 \\ \hline L3 & CID117208203 & \(-\)8.687 & \(-\)8.687 \\ \hline L4 & CID52948538 & \(-\)8.383 & \(-\)8.383 \\ \hline L5 & CID117209048 & \(-\)8.262 & \(-\)8.264 \\ \hline MEY & CID 50925477 & \(-\)7.225 & \(-\)7.946 \\ \hline \hline \end{tabular}
\end{table}