Vimala Poornima Baskar, Vajravelu Leela Kagithakara, Lathakumari Rahul Harikumar, Panneerselvam Vishnu Priya, Nair Dakshina M, Thulukkanam Jayaprakash
Department of Microbiology, SRM Medical College Hospital and Research Center, SRM Institute of Science and Technology, Kattankulathur, Chengalpattu, Tamil Nadu, India.
Department of Microbiology, SRM Medical College Hospital and Research Center, SRM Institute of Science and Technology, Kattankulathur, Chengalpattu, Tamil Nadu, India.
Comput Biol Chem. 2025 Dec;119:108564. doi: 10.1016/j.compbiolchem.2025.108564. Epub 2025 Jun 20.
This study investigates the molecular interactions between colicin A and colicin N with E-cadherin and N-cadherin-key adhesion molecules involved in cancer metastasis. Employing in silico approaches, including molecular docking using ClusPro and molecular dynamics (MD) simulations with Desmond, we evaluated the stability and binding affinities of colicin-cadherin complexes. Molecular docking results revealed favourable binding poses for both colicins, with colicin A exhibiting higher affinity than colicin N. MD simulations confirmed the stability of these interactions through root mean square deviation (RMSD) and fluctuation (RMSF) analyses, showing minimal structural perturbations throughout the simulation trajectory. Key interacting residues were identified: GLN101 and ARG201 for colicin A, and ASP90 and LYS75 for colicin N, contributing to specific protein-protein interactions. Molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) binding free energy calculations supported the formation of strong, energetically favourable complexes. Colicin A's interaction was characterized by a combination of electrostatic and van der Waals forces, whereas colicin N relied primarily on hydrophobic interactions. The findings suggest that colicin A and N can effectively bind to cadherins, potentially disrupting the epithelial-to-mesenchymal transition (EMT)-a crucial process in cancer cell dissemination. These insights support the therapeutic potential of colicin-based compounds as modulators of cadherin-mediated signalling in metastatic cancers. Our study contributes to the growing evidence of antimicrobial peptides as promising candidates for targeted cancer interventions, particularly by exploiting protein-protein interaction networks central to tumor progression.
本研究调查了大肠杆菌素A和N与E-钙黏蛋白和N-钙黏蛋白（参与癌症转移的关键黏附分子）之间的分子相互作用。我们采用计算机模拟方法，包括使用ClusPro进行分子对接以及使用Desmond进行分子动力学（MD）模拟，评估了大肠杆菌素-钙黏蛋白复合物的稳定性和结合亲和力。分子对接结果显示两种大肠杆菌素均具有良好的结合构象，其中大肠杆菌素A的亲和力高于大肠杆菌素N。MD模拟通过均方根偏差（RMSD）和波动（RMSF）分析证实了这些相互作用的稳定性，表明在整个模拟轨迹中结构扰动最小。确定了关键的相互作用残基：大肠杆菌素A的GLN101和ARG201，以及大肠杆菌素N的ASP90和LYS75，它们促成了特定的蛋白质-蛋白质相互作用。分子力学泊松-玻尔兹曼表面积（MM-PBSA）结合自由能计算支持了强的、能量上有利的复合物的形成。大肠杆菌素A的相互作用以静电和范德华力的组合为特征，而大肠杆菌素N主要依赖疏水相互作用。研究结果表明，大肠杆菌素A和N可有效结合钙黏蛋白，可能破坏上皮-间质转化（EMT）——癌细胞扩散中的关键过程。这些见解支持了基于大肠杆菌素的化合物作为转移性癌症中钙黏蛋白介导信号传导调节剂的治疗潜力。我们的研究为抗菌肽作为靶向癌症干预的有前景候选物提供了越来越多的证据，特别是通过利用肿瘤进展核心的蛋白质-蛋白质相互作用网络。
