3D Structure protein configuration

After loading the protein structure, complete the detailed configuration for Receptor, Binding site, and Box size.

Configuring the Receptor

To define the receptor binding site, go to the Receptor tab and select the components that make up the binding site.

1. Protein Chain Selection

Select one or more chains that make up the binding site.
While selecting all chains is possible, it is recommended that you select only the chains that make up the binding site for ease of use.
If you have selected a ligand, you can use the left 3D viewer to select the chains adjacent to the ligand.
This example selected chains A and D adjacent to the ligand as components.

2. Cofactor Selection

Scroll down to find the cofactor section.
The second part contains information about cofactors. If a cofactor is located near the binding site and may influence drug binding, select it.
HyperLab automatically recognizes and selects ligands and cofactors, but there can be exceptional cases, so please ensure the settings are correct.
In this example, the cofactors A-MG-201, A-GCP-202, D-MG-201, and D-GCP-202 are present but were not selected because they are located far from the binding site.

If you want to see the details of cofactors' binding information, click the magnifying glass icon next to each component's name.

In the case of a multichain PDB structure, cofactors may be present in each protein chain. Please ensure that the cofactors you intend to use are located at the binding site of the selected protein.

The cofactor list contains ligands as well. Selecting a ligand as a cofactor may lead to incorrect results.

Please ensure that ligands are deselected in the cofactor list.

3. Water molecule selection

Scroll down to find the water molecule section.
If you have loaded a protein structure using a PDB ID, it often includes water molecules. The position of these water molecules can be important, and if they significantly affect the actual ligand interactions, you can include them.
In the example above, water molecules do not influence the target protein-ligand interactions, so they were not selected.

Binding Site Settings

The process involves selecting the components of the target protein's binding site. You can choose various elements that might influence protein-drug binding, such as binding site residues, cofactors, and water molecules.

When you load a protein structure, as shown in the figure below, you can see the 3D structure of the protein in the 3D viewer on the right and information for setting up the binding site in the lower section. In the Binding site tab on the right, you can set the location and size of the binding site.
There are three methods to set up the binding site.

METHOD 1. Configuring with ligands bound to the protein structure

Configure the binding sites by selecting ligands bound to the protein from the imported structure.
In the Ligands section, when you select the ligand to be used as a binding site, the ligand structure and binding site box will appear automatically.
The example shows how we configured the binding site based on the selected ligand A-R6W-203.

METHOD 2. Configuration of the binding site based on residues

It is the configuration of the binding site box by selecting one of the residues that make up the binding site.
This method can be used to define the binding site using an approximated box approach.
When we click on Select residues, we can see the residues that make up each chain.
When we select the residues that make up the binding site, we can see the residue structure and binding site configuration box in the 3D viewer.
If the generated box is too small to use, you can configure the binding site by selecting multiple residues.
By clicking on Select multiple, we could choose two or more residues to the configure binding site.

he binding site box configured using residue selection may not accurately represent the actual binding site. Please refer to the section on adjusting box location and size to fine-tune your binding site box as needed.

METHOD 3. Upload binding site ligand to configure binding site

This method configures the binding site box using a file containing ligand structure information. It can be used when you have a structure file of a ligand bound to the binding site.
By clicking on Ligand upload in the upload section, the Select a file icon is activated.
After selecting the ligand location file and clicking Open, the ligand structure will appear alongside the protein structure, and the binding site box will be displayed as well.

The supported ligand location file extensions are: PDB, SDF, MOL2

Please note that the ligand is located in the binding site before proceeding to the next step.

Fine-tuning the binding site box

After configuring the binding site box, you can also adjust its location and size in the Box size information section.

You can directly input numbers for Center and Box size by clicking on them, or adjust the values in 1.0 Å increments by clicking the up and down arrows to the right of each number.

It's advisable to define the size of the box that determines the binding site by considering the size of the molecule you want to predict. We recommend using the default settings for defining the binding site using a typical protein-drug binding structure.

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