System Preparation Using Discovery Studio
Introductions
Discovery Studio™ is a professional life science molecular simulation software. The main functions of DS currently include: protein characterization (including protein-protein interactions), homology modeling, molecular mechanics calculations and molecular dynamics simulations, structure-based drug design tools (including ligand-protein interactions, novel drug design and molecular docking), small molecule-based drug design tools (including quantitative conformational relationships, pharmacophore, database screening, ADMET), and combinatorial library design and analysis. In this chapter, CD ComputaBio provides you with a tutorial on DS for small molecule ligand and protein preparation. We will present a selection of content for you to choose from.
- Mapping of small molecule ligands
- Structure optimization
- Energy optimization
- Protein download, import and pre-processing.
Tutorials
- Preparation of small molecule ligands
1. Draw the small molecule structure
In Discovery Studio (DS), you can build the molecular structure directly, or you can use other drawing software to draw it and then import it to DS to open it. (It is recommended to use ChemOffice software to draw small molecules and convert them to 3D structures and save them in .mol2 format) ① Click View>Toolbars>Sketching to bring up the Sketching function. Then create a new molecular window for drawing the structure, or click on File>New>Molecular Window.
You can change the atom type by selecting a carbon atom and choosing the menu bar Chemistry>Element.
Afterwards, select the menu bar Structrue>Clean Geometry to optimize the geometric 3D structure of the compound.
2. Small molecule ligand structure optimization
In the tool browser, expand Small Molecules>Prepaare or Filter Ligands>Prepare Ligands to open the corresponding process parameter setting panel; set the Input Ligands parameter structures:All, which means that all small molecules are processed, and the rest of the parameters generally set the default values.
After the parameters are set, click Run to run the task, which takes a little time to complete.
After the task is completed, the following window pops up, click Report to open the report interface, and you can see some processing information.
Click View Results to observe the structure of the processed molecules, at this time the processing of small molecules is completed.
1. Import of protein structure
① Download directly from PDB database through DS
You need computer network, click File>Open URL in the menu bar, the following dialog box will appear, directly enter the protein ID number (PDB number) and click Open.
② Import the protein crystal structure database from PDB after downloading
PDB database URL: http://www.rcsb.org/
wWe take c estrogen receptor as an example here, and download its crystal structure with the number 1A52. After opening the PDB URL, enter 1A52 in the search box and click Go.
We can see the crystal structure on the search result such as resolution, source, sequence, eutectic compound and other related information. Click Dowload Files>PDB Format to download the PDB format file of the protein crystal structure; then open the downloaded local file directly from File.
2. Protein structure processing
Select the water molecule Water from the system view, and click Delete to delete it (water molecules are generally not kept unless there is a special need, such as water molecules as a bridge between protein and ligand).
Subsequently, we need to process the protein to remove protein polymorphs, supplement non-intact amino acid residues, hydrogenate the protein, etc. In the tool browser, click Macromolecules>Prepare Protein>Clean Protein to complete the processing of the protein.
In addition, you can change the display type, color, lighting, etc. of the protein by right-clicking in the display window and selecting Display Style, which you can change as you wish.
The above is the tutorial of using Discovery Studio software for small molecule ligand and protein preparation brought to you by CD ComputaBio.
Related Services
Molecular Docking Service
Protein Structure Modeling Service
* For Research Use Only.
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