Kajian Penambatan Molekul Dan Simulasi Dinamika Molekul Turunan Quercetin Terhadap Extracellular Signal-Regulated Kinase 2 (ERK2) Sebagai Kandidat Antikanker

Nanda Ayu Pamuja, Prof. Dr. Rer. Nat. Harno Dwi Pranowo, M.Si. ; Prof. Drs. Bambang Purwono, M.Sc., Ph.D.

2026 | Skripsi | KIMIA

Kajian penambatan molekul dan simulasi dinamika molekul turunan quercetin terhadap Extracellular Signal-Regulated Kinase 2 (ERK2) sebagai kandidat antikanker telah dilakukan. Tujuan dari penelitian ini adalah mengidentifikasi potensi aktivitas penghambatan turunan quercetin terhadap protein Extracellular Signal-Regulated Kinase 2 (ERK2) sebagai reseptor target pada jalur MAPK/ERK, serta menganalisis kestabilan kompleks protein–ligan yang terbentuk. Kajian dilakukan secara in silico melalui penambatan molekul untuk mengevaluasi afinitas pengikatan dan interaksi ligan pada sisi aktif ERK2, kemudian dilanjutkan dengan simulasi dinamika molekul terhadap kompleks terbaik.

Preparasi ligan dan protein dilakukan melalui minimisasi energi menggunakan YASARA, sedangkan penambatan molekul menggunakan metode VINA. Hasil menunjukkan seluruh turunan quercetin berinteraksi dengan ERK2 melalui ikatan hidrogen konvensional, dengan residu kunci Lys54 yang konsisten terlibat. Turunan F memiliki energi ikatan paling rendah sebesar -10,287 kkal/mol, menunjukkan afinitas pengikatan tertinggi dibandingkan senyawa lainnya. Simulasi dinamika molekul selama 100 ns menunjukkan bahwa kompleks ERK2–turunan F stabil berdasarkan parameter RMSD, RMSF, dan radius of gyration (Rg). Hasil ini mengindikasikan bahwa turunan F berpotensi sebagai inhibitor ERK2 yang lebih efektif dibandingkan quercetin, sehingga berpeluang dikembangkan sebagai kandidat antikanker.

A study of the binding properties and molecular dynamics simulations of quercetin derivatives against Extracellular Signal-Regulated Kinase 2 (ERK2) as a potential anticancer agent has been conducted. The objective of this study was to identify the potential inhibitory activity of quercetin derivatives against the Extracellular Signal-Regulated Kinase 2 (ERK2) protein as a target receptor in the MAPK/ERK pathway, as well as to analyze the stability of the resulting protein ligand complex. The study was conducted in silico via molecular docking to evaluate binding affinity and ligand interactions at the active site of ERK2, followed by molecular dynamics simulations of the best-fitting complex.

Ligand and protein preparation was performed via energy minimization using YASARA, while molecular docking employed the VINA method. Results showed that all quercetin derivatives interacted with ERK2 via conventional hydrogen bonds, with the key residue Lys54 consistently involved. Derivative F had the lowest binding energy of -10.287 kcal/mol, indicating the highest binding affinity compared to the other compounds. Molecular dynamics simulations over 100 ns showed that the ERK2–derivative F complex is stable based on RMSD, RMSF, and radius of gyration (Rg) parameters. These results indicate that derivative F has the potential to be a more effective ERK2 inhibitor than quercetin, thus offering potential for development as an anticancer candidate.

Kata Kunci : ERK2, molecular docking, molecular dynamics simulation, quercetin