Defrin Defrin, Arif Birru, Kevin Cuandra, Ratna Puspita, I. Widnyana, Nasya Aqilah, Arzita Fadhilla, Winka Suwardjo, Amanda Amalia, Kalaj Haq, Tirza Amaris, Feroz Aldino, Shabrina Ekitasari, Bernice Sirait, Nathania Kristaningtyas, Rizka Wilanda, Made Ananda
Background: Placental syndromes—encompassing pregnancy loss, preterm birth, gestational diabetes mellitus, and preeclampsia—have been strongly linked to dysregulated inflammatory responses at the maternal–fetal interface. This study aims to explore the potential of peptides derived from the coelomic fluid of Echinometra lucunter targeting the inflammatory cytokines involved in placental syndromes using in silico approaches. Methods: The 3D molecular structure of peptides was modeled using the UCSF Chimera application. The absorption, distribution, metabolism, and excretion (ADMET) properties were analysed using SwissADME and the ProTox web server. The PerMM web server was used to estimate membrane permeability. Crystal structures of target proteins—including c-Met, Interleukin-1β (IL-1β), Interleukin-10 (IL-10), Macrophage Migration Inhibitory Factor (MIF), Platelet-Derived Growth Factor (PDGF), and TNF-Related Apoptosis-Inducing Ligand (TRAIL)—were obtained from the Protein Data Bank Japan (PDBj). Molecular docking and structural visualization were conducted using Molecular Operating Environment (MOE) software, while molecular dynamics simulations were subsequently performed using the YASARA Dynamics software to assess the stability and conformational behavior of the ligand-receptor complexes. Results: Peptide A was selected based on favorable ADMET properties. Molecular docking results revealed that Peptide A exhibits low binding affinities toward pro-inflammatory mediators, including TRAIL (–10.02 kcal/mol), MIF (–9.32 kcal/mol), IL-1β (–8.29 kcal/mol), and PDGF (–10.44 kcal/mol). Furthermore, Peptide A showed potential agonistic interactions with IL-10 (–10.26 kcal/mol) and c-Met (–9.27 kcal/mol), indicating a possible role in restoring anti-inflammatory and angiogenic signaling. Molecular dynamics simulations supported the stability of the peptide–receptor complexes. Conclusions: Peptide A holds promise as a dual-function therapeutic agent in placental syndromes. However, experimental validation is necessary to confirm its biological efficacy and safety. Copyright: © 2025 Defrin D et al.
Fetomaternal Division, Department of Obstetrics and Gynecology, Universitas Andalas, West Sumatra, Padang, 25171, Indonesia; Department of Obstetrics and Gynecology, Faculty of Medicine, Universitas Andalas, West Sumatra, Padang, Indonesia; Department of Medicine, Universitas Andalas, West Sumatera, Padang, 25171, Indonesia; Department of Biochemistry, Universitas Pembangunan Nasional Veteran Jakarta, Jakarta, South Jakarta, Indonesia; Department of Medicine, Universitas Pendidikan Ganesha, Bali, Singaraja, Indonesia; Department of Medicine, Universitas Airlangga, East Java, Surabaya, Indonesia; Department of Medicine, Universitas Abdurrab, Riau, Pekanbaru, Indonesia; Department of Pharmacy, Universitas Gadjah Mada, Special Region of Yogyakarta, Yogyakarta, Indonesia; Department of Medicine, Universitas Udayana, Bali, Jimbaran, Indonesia; Department of Physics, Universitas Jenderal Soedirman, Central Java, Purwokerto, Indonesia; Department of Medicine, Universitas Sebelas Maret, Central Java, Surakarta, Indonesia; Department of Medicine, Universitas Padjadjaran, West Java, Bandung, Indonesia; Department of Medicine, Faculty of Medicine Public Health and Nursing, Universitas Gadjah Mada, Special Region of Yogyakarta, Yogyakarta, Indonesia; Department of Medicine, Universitas Katolik Widya Mandala Surabaya, East Java, Surabaya, Indonesia