RT Journal Article
SR Electronic
T1 A Deep Learning Bioinformatics Approach to Modeling Protein-Ligand Interaction with cryo-EM Data in 2021 Ligand Model Challenge
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.05.27.493799
DO 10.1101/2022.05.27.493799
A1 Giri, Nabin
A1 Cheng, Jianlin
YR 2022
UL http://biorxiv.org/content/early/2022/11/22/2022.05.27.493799.abstract
AB Elucidating protein-ligand interaction is crucial for studying the function of proteins and compounds in an 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 uses a deep learning method to predict the structure of proteins from cryo-EM maps, which is averaged with a reference (template) structure of the proteins to produce a combined structure to add ligands. The ligands are then identified and added into the structure to generate a protein-ligand complex structure, which is further refined. The method based on the deep learning prediction and template-based modeling 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. The source code, data, and instruction to reproduce the results are open sourced and available on GitHub repository : https://github.com/jianlin-cheng/DeepProLigandCompeting Interest StatementThe authors have declared no competing interest.cryo-EMCryogenic electron microscopy