Covalent
Overview
HyperLab’s Covalent feature is designed to support the entire covalent drug discovery workflow within a single platform—without the need for complex reaction setup or external tools.
This page provides an overview of the overall configuration and workflow required to use the Covalent feature. For detailed instructions on each function, please refer to the dedicated guides for each step.
Covalent Workflow at a Glance
Covalent-related workflows in HyperLab can be used in the following sequence:
Configure a covalent target protein
Perform screening using covalent-specific libraries
Predict covalent binding for individual molecules
Visualize covalent binding structures in the 3D Viewer
Design molecules based on binding results
This represents a typical end-to-end workflow for covalent research. Depending on your research goals, you may selectively use only the required steps.
1. Protein Setup (Add Covalent Protein)
To begin covalent research, registering a covalent-type target protein is required. Please add a COV-type protein from the Protein Management menu.
HyperLab provides two types of proteins for covalent research:
COV 3D Structure Type
Load a reported 3D structure using a PDB ID or UniProt ID
Perform covalent docking based on a fixed protein structure
Suitable for binding prediction and screening of covalent compounds for targets with experimentally determined structures
COV Sequence Type
Generate a protein structure by searching for a protein or directly entering an amino acid sequence
Use the Co-folding feature to predict more accurate protein–ligand complex structures
Suitable for early-stage covalent drug discovery when experimental structures are unavailable
Target Residue Configuration (Required)
When registering a covalent protein, specifying the target residue for covalent bond formation is required. All subsequent covalent screening and binding calculations are performed based on this residue.
Non-covalent Protein Usage (Optional)
If needed, non-covalent proteins can also be registered to compare covalent results with non-covalent binding characteristics.
Both of the following non-covalent protein types are supported:
3D Structure type
Sequence type
2. Covalent Screening (Library-based Screening)
HyperLab provides dedicated screening libraries designed specifically for covalent reactions.
The covalent screening workflow is as follows:
Activate a Covalent 3D Structure–type protein in Bench
Click the Screening button
Covalent libraries compatible with the target residue of the active protein are automatically filtered and displayed
Select one or more libraries and run screening
Review screening results
Once screening is complete, the Warhead applied to each molecule can be reviewed.
By enabling Bench > Fields > Covalent > [Screened Protein] Warhead, you can directly view the applied Warhead for each molecule in the table.
3. Covalent Binding (Individual Molecule–based Prediction)
Covalent Binding allows you to directly predict covalent binding potential for individual molecules.
The basic workflow is as follows:
Activate a Covalent-type protein in Bench
Upload molecule files or add individual molecules using the + Molecule/Data button
Select molecules and run Hyper Binding
Specify the molecular region to be used as the Warhead
Select a Product form
If no suitable Product form is available, you can draw and add one manually
Review the binding score after calculation is complete
By enabling Bench > Fields > Covalent > [Covalen Protein] Warhead, you can directly view the applied Warhead for each molecule in the table.
4. 3D Viewer (Visualizing Covalent Binding Structures)
Results from Covalent Binding or Screening can be visually inspected in the 3D Viewer.
Select the molecule you want to inspect and click 3D View
Review the protein–ligand complex structure with the covalent bond formed
Within the Viewer:
2D Ligand panel shows the Reactant form
2D Diagram panel shows the Product form
This allows direct comparison of molecular structures before and after the covalent reaction.
5. Hyper Design (Molecule Design Based on Covalent Results)
You can perform follow-up molecule design based on covalent binding results.
Click Start Hyper Design from a Covalent Binding result
Move to the design page
Design is enabled for regions excluding the Warhead and adjacent binding sites
This allows structural exploration to improve activity, selectivity, and physicochemical properties while maintaining the covalent bond.
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