Molecular Docking of Interaction between E-Cadherin Protein and Conformational Structure of Cyclic Peptide ADTC3 (Ac-CADTPC-NH2) Simulated on 20 ns

Abstract

A r t i c l e I n f o A b s t r a c t Keywords:ADTC3, E-cadherin domain EC1, Gromacs, dockingThe treatment of diseases that attack the brain is very difficult, because the delivery of drug molecules to the brain is often hindered by the molecules of blood-brain barrier (BBB). Thus, it was developed the new method using synthetic peptide which derived from the amino acids sequence of cadherin and ADTC3 predicted able to modulate the intercellular junction peptide. The intermolecular interaction between ADTC3 and Ecadherin is hypothesized as the driving force of modulation. In this research have been calculated the interaction energy between ADTC3 and E-cadherin. The method used in this research is molecular dynamics (MD) and molecular docking. The results show that cyclic peptide ADTC3 (Ac-CADTPC-NH2) simulated for 20 ns (20,000 ps) has considerable interaction with EC1 domain of E-cadherin which have the binding energies -31.55 kJ.mol -1 and inhibition constant Ki 2.96 μM at the 4487 conformation. This highly interaction energy was predicted as the driving force in modulating intercellular junctions. The binding site of E-cadherin reside on amino acid residues Asp1, Trp2, Val3, Ile4, Lys25, Met92 in the adhesion arm-acceptor pocket region. A b s t r a kKata kunci: ADTC3, E-cadherin domain EC1, Gromacs, docking Pengobatan penyakit yang menyerang otak sangat sulit dilakukan karena penghantaran molekul obat menuju otak terhalang oleh molekul-molekul blood-brain barrier (BBB). Untuk mengatasinya telah dikembangkan metode baru dengan memodulasi junction antar sel menggunakan peptida. Salah satu peptida yang diperkirakan mampu memodulasi adalah ADTC3, yang diturunkan dari susunan asam amino kadherin. Modulasi terjadi diduga karena interaksi antara ADTC3 dengan E-kadherin. Pada penelitian ini telah dihitung energi interaksi antara ADTC3 dengan E-kadherin. Metode yang digunakan adalah dinamika molekul (DM) dan molecular docking. Hasil penelitian menunjukkan bahwa peptida siklik ADTC3 (Ac-CADTPC-NH2) hasil simulasi 20 ns (20.000 ns) berinteraksi kuat dengan domain EC1 E-kadherin dengan energy binding sebesar -31,55 kJ.mol -1 dan tetapan inhibisi Ki sebesar 2,96 µM pada konformasi ke-4487. Interaksi yang kuat ini diperkirakan sebagai daya penggerak memodulasi junction antar sel. Interaksi antara ADTC3 dengan E-kadherin terjadi pada situs residu Ekadherin Asp1, Trp2, Val3, Ile4, Lys25, Met92 yang berada pada daerah adhesion armacceptor pocket.

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