Besli Nail, Bulut Halil İbrahim, Onaran İlhan, Carmena-Bargueño Miguel, Pérez-Sánchez Horacio
Department of Medical Biology, Hamidiye School of Medicine, University of Health Sciences, Istanbul, Turkey.
Faculty of Medicine, Medical Program, Istanbul University-Cerrahpasa, Istanbul, Turkey.
Mol Divers. 2025 Feb;29(1):61-71. doi: 10.1007/s11030-024-10832-w. Epub 2024 Apr 8.
Cluster of differentiation 147 (CD147) is an attractive target for anticancer therapy since it is pivotal in developing and progressing several of malignant tumors in the context of its high expression levels. Although anti-CD147 antibodies by different laboratories are designed for the Ig-like domains of CD147, there is a demand to provide priority among these anti-CD147 antibodies for developing of therapeutic anti-CD147 antibody before experimental validations. This study uses molecular docking and dynamic simulation techniques to compare the binding modes and affinities of nine antibody models against the Ig-like domains of CD147. After obtaining the model antibodies by homology modeling via Robetta, we predicted the CDRs of nine antibodies and the epitopes of CD147 to reach more accurate results for antigen affinity in molecular docking. Next, from HADDOCK 2.4., we meticulously handpicked the most superior model clusters (Z-Score: - 2.5 to - 1.2) and identified that meplazumab had higher affinities according to the success rate as the percentage of a scoring scale. We achieved stable simulations of CD147-antibody interaction. Our outcomes hold hypothetical importance for further experimental cancer research on the design and development of the relevant model antibodies.
分化簇147(CD147)是抗癌治疗的一个有吸引力的靶点,因为它在多种恶性肿瘤的发生和发展过程中起着关键作用,且表达水平较高。尽管不同实验室设计的抗CD147抗体是针对CD147的免疫球蛋白样结构域,但在进行实验验证之前,需要在这些抗CD147抗体中确定开发治疗性抗CD147抗体的优先级。本研究使用分子对接和动态模拟技术比较了九种抗体模型与CD147免疫球蛋白样结构域的结合模式和亲和力。通过Robetta进行同源建模获得模型抗体后,我们预测了九种抗体的互补决定区(CDR)和CD147的表位,以便在分子对接中获得更准确的抗原亲和力结果。接下来,从HADDOCK 2.4中,我们精心挑选了最优秀的模型簇(Z分数:-2.5至-1.2),并根据成功率(作为评分量表的百分比)确定美普单抗具有更高的亲和力。我们实现了CD147-抗体相互作用的稳定模拟。我们的结果对于进一步开展相关模型抗体设计和开发的实验性癌症研究具有假设性的重要意义。