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Updated: Jun 5, 2026
08:31
Biosensor-based High Throughput Biopanning and Bioinformatics Analysis Strategy for the Global Validation of Drug-protein Interactions
Published on: December 1, 2020
Sequence-based Drug-Target Binding Site Pretraining Enables Cryptic Pocket Detection and Improves Binding Affinity
Shuo Zhang1,2, Li Xie1, Daniel Tiourine1
1Department of Computer Science, Hunter College, The City University of New York, New York, 10065, NY, USA.
Biorxiv : the Preprint Server for Biology
|June 4, 2026
Summary
ProMoNet, a novel sequence-based framework, enhances protein-ligand binding prediction by modeling microscale interactions and protein dynamics. This approach accelerates drug discovery by improving predictions of binding affinity and kinetics.
Area of Science:
- Computational biology
- Drug discovery
- Bioinformatics
Background:
- Predicting protein-ligand binding is crucial for drug discovery.
- Existing methods struggle with data integration, protein dynamics, and microscale interactions.
Purpose of the Study:
- Introduce ProMoNet, a sequence-based pre-training and fine-tuning framework.
- Enhance prediction of protein-ligand binding characteristics like affinity and kinetics.
Main Methods:
- Leveraged protein and molecular foundation models for expanded data coverage.
- Developed a pre-training module using protein-ligand binding site prediction.
- Designed a fine-tuning module to transfer pre-trained knowledge.
Main Results:
- Pre-training module effectively models microscale interactions and protein dynamics, including cryptic binding sites.
- Outperformed or matched state-of-the-art structure-based methods in binding site identification.
- Achieved superior performance in predicting binding affinity and kinetics.
Conclusions:
- ProMoNet offers a highly efficient and effective sequence-based approach for protein-ligand binding prediction.
- Demonstrated potential for broad applications in accelerating drug discovery.
Related Concept Videos
01:49Conserved Binding Sites
Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally analyses the...
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally analyses the...
01:49Conserved Binding Sites
Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally analyses the...
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally analyses the...
02:40Ligand Binding Sites
Proteins are dynamic macromolecules that carry out a wide variety of essential processes; however, the activities of most proteins depend on their interactions with other molecules or ions, known as ligands.
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
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01:26Drug Discovery: Overview
Drug discovery is a multifaceted process involving extensive screening, testing, and optimization of lead compounds to identify potential new drugs for therapeutic use. It combines several approaches, including screening large numbers of natural products, chemical modification of known active molecules, identification of new drug targets, and rational design based on biological mechanisms and drug-receptor structure. These approaches are carried out in both academic research laboratories and...
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