Zuhrah Taufiqa, Kevin N. Cuandra, Daivan F.J. Setiya, Shakira, Muhammad Z. Fatahillah, Jauza A. Hanun, Faithu Arthuvachivo, Winka P. Suwardjo, Fasha P. Arkhani, Eka M. Saputri, Nadia R. Salfistra, Hilmi A. Haq, Vitasigi D. Febyaningrum
Obesity is a complex and multifactorial global health problem driven by dysregulated appetite control, lipid metabolism, and energy homeostasis. Current therapeutic strategies remain limited by modest long-term efficacy, safety concerns, or restricted accessibility, highlighting the need for novel multi-target approaches. Marine-derived peptides have emerged as promising candidates due to their structural diversity, favourable safety profiles, and capacity to modulate multiple biological pathways. This study employed a comprehensive in silico approach to evaluate peptides derived from Lytechinus variegatus as potential anti-obesity agents. Peptide sequences from Lytechinus variegatus were prepared in MOE v2022.2 after retrieval from published datasets and the RCSB Protein Data Bank. ADME properties were predicted using SwissADME, and toxicity was evaluated with ProTox v3.0. Molecular docking was performed in MOE 2022.02. Molecular dynamics simulations (50 ns) were conducted in YASARA Dynamics. Membrane permeability was predicted using the PerMM web server under physiological conditions. Among the evaluated peptides, peptide 7 consistently demonstrated the most favourable binding affinities across all targets, outperforming reference inhibitors and maintaining stable interactions with acceptable RMSD values. Molecular dynamics analyses confirmed stable complex formation, particularly with FTO, PPARγ, and PTP1B. Peptide 7 exhibited high solubility, non-toxicity, and minimal predicted interaction liabilities. The PMF profile revealed a pronounced energy barrier at the bilayer centre, indicating unfavourable penetration into the membrane core and preferential localisation in the aqueous or interfacial regions. These findings identify peptide 7 as the most promising anti-obesity candidate among Lytechinus variegatus–derived peptides and support further experimental validation. © 2026 Taufiqa et al.
Department of Medicine, Faculty of Medicine, Universitas Negeri Padang, Bukittinggi, Indonesia; Department of Medicine, Faculty of Medicine, Universitas Andalas, Padang, Indonesia; Department of Medicine, Faculty of Medicine, Universitas Islam Indonesia, Sleman, Indonesia; Department of Medicine, Faculty of Medicine, Universitas Malikussaleh, Aceh, Lhoksemauwe, Indonesia; Department of Medicine, Faculty of Medicine, Universitas Sebelas Maret, Surakarta, Indonesia; Department of Pharmacy, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta, Indonesia; Department of Pharmacy, Faculty of Mathematics and Natural Sciences, Universitas Sebelas Maret, Surakarta, Indonesia
