*4.4. Pharmacophore Studies*

The pharmacophore model was carried out using Discovery Studio 4.0 software. The protocol of receptor-ligand pharmacophore generation was applied. This protocol used the co-crystallized ligand of MMP-9 (PDB ID: 1GKC) as a reference molecule. The tested compounds were used as a training set. In this protocol, we used the following

features in pharmacophore generation: (i) hydrogen bond donor (HBD), (ii) hydrogen bond acceptor (HBA), (iii) hydrophobic aliphatic (HA), (iv) hydrophobic aromatic (HAr), and ring aromatic (RA). Then, the ligand pharmacophore mapping protocol was used in the virtual screening process. The most predictive model was used as 3D queries to identify compounds with high fit values [36–39].

**Supplementary Materials:** The following supporting information can be downloaded at: https:// www.mdpi.com/article/10.3390/molecules27113584/s1, Figure S1. Atenolol properties throughout 50 ns simulation in complex with MMP-2; Figure S2. Ampicillin properties throughout 50 ns simulation in complex with MMP-9; Figure S3. RMSF of atenolol throughout 50 ns simulation in complex with MMP-2; Figure S4. RMSF of ampicillin throughout 50 ns simulation in complex with MMP-9; Table S1. Fit values of the full library on MMP-9 pharmacophore.

**Author Contributions:** A.B.: Conceptualization, Investigation, Visualization, Writing—original draft, Writing—review & editing; M.A.E.: Methodology, Software, Validation and Writing—review & editing; E.Y.S.: Validation, Formal analysis, Funding acquisition, Writing—review & editing; A.A.A.-K.: Validation, Formal analysis, Funding acquisition, Writing—review & editing; M.O.A.: Data curation, Validation and Writing—review & editing; A.H.A.: Validation, Formal analysis, Funding acquisition, Writing—review & editing; M.H.A.: Validation, methodology, Writing—review & editing; A.B.M.M.: Conceptualization, Validation, Investigation, Writing—review & editing; H.E.: Methodology, Software, Validation and Writing—original draft. All authors have read and agreed to the published version of the manuscript.

**Funding:** Taif University Researchers Supporting, Project number (TURSP-2020/330), Taif University, Taif, Saudi Arabia, and Deanship of Scientific Research at Umm Al-Qura University, Grant Code: (22UQU4331100DSR13).

**Institutional Review Board Statement:** Not applicable.

**Informed Consent Statement:** Not applicable.

**Data Availability Statement:** Supplementary Materials are provided.

**Acknowledgments:** The authors would like to introduce their appreciation and thanks to the Taif University Researchers Supporting, Project number (TURSP-2020/330), Taif University, Taif, Saudi Arabia. The authors would like to thank the Deanship of Scientific Research at Umm Al-Qura University for supporting this work by Grant Code: (22UQU4331100DSR13).

**Conflicts of Interest:** The authors declare no conflict of interest.
