Moe version 2020 09

The two compounds nuciferine (1) and norcoclaurine (2) isolated from the seeds of N. nucifera along with glimepiride were docked into the active site of α-glycosidase and α-amylase. The PDB structures of these enzymes were downloaded from protein data bank by their respective PDB codes, i.e., 5HQA and 1BVN, respectively. Next, the structural coordinates of both the enzymes were subjected to a Molecular Operating Environment software (MOE, Version 2020-09, Chemical Computing Group, Montreal, QC, Canada), package for preparation to obtain a minimum energy conformation of the enzymes for docking purposes. Finally, molecular docking was carried out for the optimized structures of receptors utilizing the default molecular docking standard protocol in MOE. The top-ranking docked complex based on the protein–ligand interaction (PLI) profile was chosen for exploration of the binding mode. Pymol was used for protein–ligand interaction and visualization.

The structure was determined by molecular replacement using the published crystal structure of the Aurora-A–MYCN complex (PDB entry 5g1x; Richards et al., 2016 ▸ ) as a search model. Due to the lack of electron density for the terminal regions of the MYCN peptide, it was truncated in the search model to residues 72–89 and molecular replacement was repeated. The mutations at Lys339 of Aurora-A and Asn85 of MYCN and the linker were built in MOE (version 2020.09; Chemical Computing Group, Montreal, Canada) and restraints for the maleimidopropionic acid linker were derived using AceDRG (Long et al., 2017 ▸ ). The covalent connections between the maleimidopropionic acid moiety and residues Cys339 of Aurora-A and Lys85 of MYCN were defined during refinement by using geometry restraints in phenix.refine (Liebschner et al., 2019 ▸ ). Parameters were copied from analogous moieties in the REFMAC monomer libraries (Supplementary Table S1). The Bicine molecule was fitted to the electron density in Coot (Emsley et al., 2010 ▸ ). Refinement statistics are summarized in Table 4 ▸.

Docking analysis of YW7 to ANXA2 protein was performed by MOE Version 2020.09 (Chemical Computing Group Inc., Montreal, Canada) according to compute energy scoring functions. The structure of ANXA2 (PDB:4HRE) was downloaded from the PDB database (https://www.rcsb.org/) and YW7 was generated from the Protein Builder Module of MOE. The spatial structure of YW7 was optimized by the Energy Minimize Function of MOE. Docking was conducted automatically by default parameters. The structure with the lowest free energy of binding was selected.