Iraninan Biology Society Journal of Cellular and Molecular Research (Iranian Journal of Biology) 2383-2738 37 4 2025 02 19 The RGD sequence improves the binding of collagen IV-derived peptides to integrins: an in silico study The RGD sequence improves the binding of collagen IV-derived peptides to integrins: an in silico study 402 418 2263 FA Reyhane Chamani Department of Biology, Yazd University, Yazd, Iran 0000-0002-5160-0159 Mohsen Namnabat Department of Biology, Yazd University, Yazd, Iran 0000-0002-7181-9772 Mohammad Hossein Taleqani Department of Biology, Yazd University, Yazd, Iran 0000-0002-6976-4901 Aylar Imanpour Department of Fisheries, Faculty of Natural Resources, Urmia University, Urmia, Iran 0000-0002-6539-9185 Journal Article 2022 12 09 RGD-binding integrins are receptors overexpressed in various tumors and play an important role in their growth, angiogenesis and metastasis. Therefore, the design of inhibitors containing RGD has been of great interest to inhibit integrins and treat cancer. Arrestan, canstatin, and tumstatin, angiogenesis inhibitors derived from collagen IV, act by binding to integrins and inhibiting their signaling pathway. In a study, it was shown that peptides derived from arresten (A), canstatin (C), and tumstatin (T) are capable of inhibiting angiogenesis and tumor growth, and peptide C is more active than the other two peptides. In the present study, the RGD sequence was added to the end of the mentioned peptides and their structure was analyzed with the help of molecular dynamics simulation and their interaction with αvβ3, αvβ6, αvβ8, α5β1, and α6β1 integrins was analyzed using AutoDock 4 software. The results showed that the addition of RGD changes the secondary structures and reduces structural fluctuations in peptides. Also, peptides with RGD were bound to all integrins with a more negative binding energy, and the binding energy of the CRGD peptide was more negative than others. Therefore, RGD peptides can be suggested for further laboratory investigations. Overall, the results of this study can be useful for the design of integrin inhibitors to inhibit angiogenesis and tumor growth. RGD-binding integrins are receptors overexpressed in various tumors and play an important role in their growth, angiogenesis and metastasis. Therefore, the design of inhibitors containing RGD has been of great interest to inhibit integrins and treat cancer. Arrestan, canstatin, and tumstatin, angiogenesis inhibitors derived from collagen IV, act by binding to integrins and inhibiting their signaling pathway. In a study, it was shown that peptides derived from arresten (A), canstatin (C), and tumstatin (T) are capable of inhibiting angiogenesis and tumor growth, and peptide C is more active than the other two peptides. In the present study, the RGD sequence was added to the end of the mentioned peptides and their structure was analyzed with the help of molecular dynamics simulation and their interaction with αvβ3, αvβ6, αvβ8, α5β1, and α6β1 integrins was analyzed using AutoDock 4 software. The results showed that the addition of RGD changes the secondary structures and reduces structural fluctuations in peptides. Also, peptides with RGD were bound to all integrins with a more negative binding energy, and the binding energy of the CRGD peptide was more negative than others. Therefore, RGD peptides can be suggested for further laboratory investigations. Overall, the results of this study can be useful for the design of integrin inhibitors to inhibit angiogenesis and tumor growth. https://cell.ijbio.ir/article_2263_26505e0494662534f633586941b77d0c.pdf