Publication: 2D LIGAND-BASED SIMILARITY SEARCH, MOLECULAR DOCKING AND CLUSTERING OF APPROVED DRUGS DATABASES FOR IDENTIFICATION OF POTENTIAL PORPHYROMONAS GINGIVALIS PEPTIDYLARGININE DEIMINASE INHIBITORS
| dc.contributor.author | IBRAHIM YALCOUYE | |
| dc.date.accessioned | 2025-11-12T04:14:01Z | |
| dc.date.available | 2025-11-12T04:14:01Z | |
| dc.date.issued | 2025 | |
| dc.description.abstract | Porphyromonas gingivalis is implicated in chronic periodontal disease and secretes virulence factors, including Porphyromonas gingivalis peptidylarginine deiminase (PPAD), which catalyzes the conversion of arginine to citrulline in proteins, leading to the production of autoantigens. These autoantigens are associated with autoimmune responses in rheumatoid arthritis (RA). Epidemiological studies suggest a link between periodontal disease and RA, highlighting the potential of PPAD inhibition as a therapeutic strategy [1,2]. The present study aims to identify potential inhibitors of PPAD through a combination of 2D ligand-based similarity search, molecular docking and clustering studies from approved drugs databases as well as structural features essential for the inhibitory activity against PPAD [2]. The study employed a ligand-based virtual screening (LBVS) approach, leveraging the SwissSimilarity web tool to perform 2D similarity searches [3]. Hit compounds identified from prior PPAD inhibitory activity studies, namely Flucytosine, Cl-Amidine, Cytarabine and Carmustine, served as query molecules for this process [5]. 15 hits with the highest similarity score under each fingerprinting method of respective query molecules were identified from the similarity search, which were subjected to molecular docking via Schrödinger Glide docking program to evaluate their binding interactions in the PPAD binding site and structural determinants [4]. 5 final hit compounds were found to have higher docking scores than that of dipeptide reference ligand (-4.913 kcal/mol) ranging between -5.487 kcal/mol to -7.076 kcal/mol. Additionally, ChemMine web tool was used to cluster compounds obtained from similarity search of respective query molecules by structural similarities. 4 out 5 final hit compounds identified from molecular docking studies were found clustered in the respective major cluster bin consisting of higher number of compounds with similar structures than the other cluster bins, thus suggesting the corresponding chemical motif that contributes to ligand recognition within the PPAD binding pocket [5]. It was generally found that structural features, particularly hydrogen bond acceptors with electronegative oxygen atoms or nitrogen atoms, aromatic ring or heterocycle, cyclic ring with hydroxyl groups are essential for the inhibition of PPAD. Indeed, this silico study has identified potential PPAD inhibitors and provided insights into the structural features that could be crucial for PPAD inhibitory activity. | |
| dc.identifier.uri | https://hdl.handle.net/20.500.14377/37249 | |
| dc.language.iso | en | |
| dc.publisher | IMU University | |
| dc.subject | Molecular Docking Simulation | |
| dc.subject | Porphyromonas | |
| dc.subject | Porphyromonas gingivalis | |
| dc.subject | Protein-Arginine Deiminases | |
| dc.subject | Ligands | |
| dc.title | 2D LIGAND-BASED SIMILARITY SEARCH, MOLECULAR DOCKING AND CLUSTERING OF APPROVED DRUGS DATABASES FOR IDENTIFICATION OF POTENTIAL PORPHYROMONAS GINGIVALIS PEPTIDYLARGININE DEIMINASE INHIBITORS | |
| dc.type | Thesis | |
| dspace.entity.type | Publication | |
| oairecerif.author.affiliation | #PLACEHOLDER_PARENT_METADATA_VALUE# |