# A New Insight into the Study of Neural Cell Adhesion Molecule (NCAM) Polysialylation Inhibition Incorporated the Molecular Docking Models into the NMR Spectroscopy of a Crucial Peptide–Ligand Interaction

## TL;DR

This study explores how to inhibit tumor cell migration by analyzing interactions between a key enzyme and ligands using molecular docking and NMR.

## Contribution

The novel approach combines molecular docking models with NMR spectroscopy to study ligand interactions for tumor migration inhibition.

## Key findings

- Molecular docking models of ST8Sia4 and ligands were predicted using AlphaFold 3 and DiffDock.
- NMR spectroscopy confirmed interactions between the polysialyltransferase domain and ligands.
- The combined strategy offers a new method for screening tumor cell migration inhibitors.

## Abstract

The expression of polysialic acid (polySia) on the neuronal cell adhesion molecule (NCAM) is called NCAM-polysialylation, which is strongly related to the migration and invasion of tumor cells and aggressive clinical status. During the NCAM polysialylation process, polysialyltransferases (polySTs), such as polysialyltransferase IV (ST8SIA4) or polysialyltransferase II (ST8SIA2), can catalyze the addition of CMP-sialic acid (CMP-Sia) to the NCAM to form polysialic acid (polySia). In this study, the docking models of polysialyltransferase IV (ST8Sia4) protein and different ligands were predicted using Alphafold 3 and DiffDock servers, and the prediction accuracy was further verified using the NMR experimental spectra of the interactions between polysialyltransferase domain (PSTD), a crucial peptide domain in ST8Sia4, and a different ligand. This combination strategy provides new insights into a quick and effective screening for inhibitors of tumor cell migration.