State Key Laboratory of Computer Architecture, Institute of Computing Technology, Chinese Academy of Sciences, Beijing, 100190, China.
Phys Chem Chem Phys. 2021 Mar 28;23(12):7066-7079. doi: 10.1039/d0cp05003b. Epub 2021 Jan 26.
Aptamers (small single strand DNA/RNAs) such as SYL3C are considered as ideal alternatives to antibodies in cancer related research studies. However, 3D structure predictions for aptamers and aptamer-protein complexes are scarce due to the high cost of experimental measurements and unreliable computer-based methods. Thus aptamers' diagnostic and therapeutic applications are severely restricted. To meet the challenge, we proposed a Martini-based aptamer-protein complex prediction protocol. By combining the base-base contact map from simulation and secondary structure prediction from various tools, improved secondary structure predictions can be obtained. This method reduced the risk of providing incorrect or incomplete base pairs in secondary structure prediction. Thus 3D structure modeling based on the secondary structure can be more reliable. We introduced the soft elastic network to the hairpin folded regions of the Martini ssDNAs to preserve their canonical structure. Using our protocol, we predicted the first 3D structure of the aptamer SYL3C and the SYL3C-EpCAM complex. We believe that our work could contribute to the future aptamer-related research studies and medical implications.
适体（如 SYL3C 的小单链 DNA/RNA）被认为是癌症相关研究中替代抗体的理想选择。然而，由于实验测量成本高和基于计算机的方法不可靠，适体和适体-蛋白复合物的 3D 结构预测仍然很少。因此，适体的诊断和治疗应用受到严重限制。为了应对这一挑战，我们提出了一种基于 Martini 的适体-蛋白复合物预测方案。通过结合模拟的碱基-碱基接触图和来自各种工具的二级结构预测，可以获得改进的二级结构预测。这种方法降低了在二级结构预测中提供不正确或不完整碱基对的风险。因此，基于二级结构的 3D 结构建模可以更加可靠。我们将软弹性网络引入到 Martini ssDNA 的发夹折叠区域，以保持其规范结构。使用我们的方案，我们预测了适体 SYL3C 和 SYL3C-EpCAM 复合物的第一个 3D 结构。我们相信我们的工作将有助于未来的适体相关研究和医学应用。
