Predicting the Most Stable Aptamer/Target Molecule Complex Configuration Using a Stochastic-Tunnelling Basin-Hopping Discrete Molecular Dynamics Method: A Novel Global Minimum Search Method for a Biomolecule Complex

This study proposed a novel global minimum search method for predicting the most stable biomolecule complex, which combines the strengths of three global minimum search methods (stochastic tunnelling, basin hopping, and discrete molecular dynamics) to efficiently improve the spatial domain search ability of the stochastic tunnelling–basin hopping (STUN–BH) method from our previous study. The epithelial cell adhesion molecule (EpCAM, PDB code: 4MZV) was used as a benchmark target molecule for the EpCAM aptamer EpA (Apt_EpA). For the most stable Apt_EpA/EpCAM complex predicted by our new method, the Apt_EpA was attached to the entangling loop fragments of the two EpCAM molecules with the most Apt_EpA residues. After the Apt_EpA/EpCAM complex had equilibrated with the water environment through a molecular dynamics simulation at 300 K for 10 ns, stable hydrogen bonds formed between the bases of Apt_EpA and EpCAM residues of the secondary structures, which included the alpha helix and beta sheet becoming less stable in the water environment. Those hydrogen bonds formed between the bases of Apt_EpA and EpCAM loop fragment residues remained stable in the water environment.