Predicting the aptamer SYL3C–EpCAM complex's structure with the Martini-based simulation protocol

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.