Unlocking ADAMTS-5: In Silico insights into TMJ proteomics and docking dynamics

Temporomandibular joint (TMJ) disorder refers to a condition involving dysfunction or pain in the jaw joint and the muscles that control jaw movement. It can affect one or both sides of the jaw and can cause various symptoms, including Jaw pain or tenderness; Difficulty or discomfort when chewing; Clicking, popping, or grating sounds in the jaw joint; Jaw locking or limited movement; Earache or pain around the ear; Headaches or migraines; Neck and shoulder pain; Swelling on the side of the face. TMJ disorder can have various causes, including injury to the jaw joint, teeth grinding or clenching (bruxism), arthritis, stress, misalignment of the jaw or teeth, and excessive gum chewing. Computer-aided drug design (CADD) comprises a range of theoretical and computational strategies employed in contemporary drug discovery. Molecular docking stands out as a key technique within CADD, aiding in the comprehension of drug-molecule interactions for rational drug design, mechanistic investigations, and the creation of stable complexes with heightened specificity and potential effectiveness. Through the docking process, valuable information regarding binding energy, free energy, and predictions of complex stability is obtained, offering significant insights into drug development endeavors.

The objective of this research was to employ docking methodology to identify potential ADAMTS-5 protein for TMJ. Four ADAMTS-5 protein inhibitors previously reported in the literature were selected, and their compound structures were obtained from the Zinc15 database. The ADAMTS-5 protein was designated as the target and optimized utilizing the RCSB Protein Data Bank. Following pharmacophore modeling, 20 novel compounds were identified, and SwissDock was utilized to dock these compounds with the target protein. A comparison was made between the binding energies of the newly discovered compounds and those of previously published molecules with the target.

The results indicated that among the 20 ZINC1846088 and ZINC33606904 exhibited the highest binding energy and displayed superior properties compared to the other molecules.

The study concluded that ZINC1846088 and ZINC33606904 exhibited greater binding affinity than the reported inhibitors of ADAMTS-5 protein. Therefore, these two molecules can be used as a potential and promising lead for the treatment of TMJ and could be employed in targeted drug therapy.

Dentistry, TMJ.