Abstract
Elucidating protein-ligand interaction is crucial for studying the function of proteins and compounds in a living organism and critical for drug discovery and design. The problem of protein-ligand interaction is traditionally tackled by molecular docking and simulation based on physical forces and statistical potentials, which cannot effectively leverage cryo-EM data and existing protein structural information in the protein-ligand modeling process. In this work, we developed a deep learning bioinformatics pipeline (DeepProLigand) to predict protein-ligand interactions from cryo-EM density maps of proteins and ligands. DeepProLigand first use a deep learning method to predict the structure of proteins from cryo-EM maps, which is averaged with a reference structure of the proteins to produced a combined structure to add ligands. The ligands are then identified and added into the structure to produce a protein-ligand complex structure, which is further refined. The method was blindly tested in the 2021 EMDataResource Ligand Challenge and was ranked first in fitting ligands to cryo-EM density maps. The results demonstrate the deep learning bioinformatics approach is a promising direction to model protein-ligand interaction on cryo-EM data using prior structural information.
Competing Interest Statement
The authors have declared no competing interest.
