Introducing membrane models for cancer cell and evaluating their functional role in response to bioactive peptides, using All-atom and Steered molecular dynamic simulations

Dabbagh Sadeghpoor, Somayyeh; Zarrabi, Mahboobeh; Balalaie, Saeed; Ramezani, Reihaneh

doi:10.22034/cmr.2025.2329

Introducing membrane models for cancer cell and evaluating their functional role in response to bioactive peptides, using All-atom and Steered molecular dynamic simulations

Document Type : Research Paper

Authors

Somayyeh Dabbagh Sadeghpoor ¹

mahboobeh zarrabi ¹

Saeed Balalaie ²

Reihaneh Ramezani ³

¹ Bioinformatic Lab, Department of Biotechnology, Faculty of Biological sciences, Alzahra University, Tehran, Iran

² Peptide Chemistry Research Institute, Khajeh Nasir Toosi University of Technology, Tehran, Iran

³ Department of ّFamily Therapy, Women Research Center, Alzahra University, Tehran, Iran

10.22034/cmr.2025.2329

Abstract

Molecular dynamic simulation provides computational insights into membrane alterations during interaction with peptides and chemical drugs. In such a case, modeling realistic bilayers is critical because the peptide-membrane interactions depend on bilayer lipid compositions. According to these facts, in this project two cancerous bilayers as static(solid) and dynamic(fluid) models, constructed and the effect of saturation degree on bilayer function was analyzed by incorporating polyunsaturated fatty acids on bilayer hydrophobic core. Then their interaction with GL13K peptide were evaluated using All-atom and Steered molecular dynamic simulations. Based on results, dynamic model, provides acceptable surface area for primary interaction, surface adsorption, and peptide penetration during 200ns than static one. The persistence of these interactions in static models changed after 50 ns of simulation and after that time, the peptide lost its dominant helical structure. Steered MD simulation, also demonstrated the high binding affinity of peptide to the surface of dynamic model. Tracking interactions during 25ns intervals, revealed the key function of Lysine5 in peptide structure and highlighted the importance of realistic model bilayers in forming stable peptide-bilayer interactions.

Keywords

Computational biology

Oncosome

Polyunsaturated fatty acids

Subjects