Protein-protein interaction prediction Protein-protein interaction prediction protein

How to prepare structures for HADDOCK? - Bonvin Lab https://www.bonvinlab.org/software/bpg/structures/ RosettaDock: Protein-protein complex docking prediction - Zhihu (zhihu.com)

To perform binding affinity prediction of the LPR1-SEPP1 complex, you can follow these steps:

1. Obtain protein structure data: First, you need to obtain crystal structure data for LRP1 and SEPP1. This can be obtained through experimental methods such as X-ray crystallography and nuclear magnetic resonance. You can search for corresponding structural data in professional databases (such as Protein Data Bank) or contact relevant researchers.

2. Prepare protein structure files: Save the obtained structural data of LRP1 and SEPP1 as files in PDB or mmCIF format. Make sure the file contains information about complete protein chains, ligands, or other interacting molecules.

3. Perform molecular docking calculations: Use molecular docking software, such as AutoDock, Vina, HADDOCK, etc., to input the structure files of LRP1 and SEPP1 for molecular docking calculations. These software can simulate interactions between proteins and ligands and generate possible complex conformations.

4. Export the complex structure: Based on the results of molecular docking calculations, select the most appropriate complex conformation and export the complex structure to a file in PDB or mmCIF format.

5. Use PRODIGY for prediction: Visit the PRODIGY website and upload the exported LRP1-SEPP1 complex structure file to the corresponding prediction tool or option. Follow the site's instructions to submit your prediction task. Prodigy Webserver (uu.nl) https://wenmr.science.uu.nl/prodigy/

6. Parse prediction results: Once the prediction task is completed, you will obtain the binding affinity prediction results of the LRP1-SEPP1 complex. Based on the results of PRODIGY, the binding strength of the complex can be evaluated.

Please note that the molecular docking software and PRODIGY mentioned in the above steps are commonly used tools, but their use may require certain computing resources and expertise. If you are not familiar with molecular docking and binding affinity prediction methods, it is recommended to seek help and guidance from professional researchers or experts in related fields.

For each molecule, you can provide the following information:

• PDB_ID: PDB ID of the target complex. This is the unique identifier of the target complex in the Protein Data Bank (PDB) database.
• ID_chain(s): Chain ID associated with each molecule in the complex. For example, if a molecule consists of chain A and chain B, you would enter "A,B" as ID_chain(s) .

When filling out the form, fill in the relevant information about Interactor 1 and Interactor 2 into the corresponding fields. At the same time, you can also provide the temperature (in degrees Celsius) so that PRODIGY takes the effect of temperature into account when predicting binding affinity.

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The following are the general steps for protein-ligand molecular docking using AutoDock, Vina, and HADDOCK molecular docking software :

1. Prepare protein and ligand structure files, which can be downloaded from the PDB database. If necessary, the structure must be optimized to ensure the integrity and accuracy of the molecular structure.

2. Preprocess molecules: including adding hydrogen atoms, removing water molecules, specifying atom types and charge states, etc. These steps can be completed using automated tools or professional software, such as AutoDockTools or OpenBabel, etc.

3. Determine the search space: When performing molecular docking, a search space needs to be defined to limit the motion range of the molecules. The search space is usually determined by a reference point (such as the active site) and the size of the space. Search spaces can be defined using files in pdbqt format.

4. Run molecular docking calculation: Use molecular docking software to input the preprocessed protein and ligand structure files, specify the search space and other parameters, and run the program for calculation. The calculation results will generate a series of possible complex conformations.

• AutoDock: The input files of AutoDock mainly include four aspects: protein files, ligand files, search parameter files and termination condition files. The Lamarckian genetic algorithm was used to search for the most likely complex conformation by evaluating the molecular docking free energy of each conformation.

• Vina: The input files of Vina mainly include protein files, ligand files and parameter files. It uses a gradient descent algorithm to search for the most likely complex conformation by evaluating the binding free energy of each conformation.

• HADDOCK: The input files of HADDOCK include protein PDB files, ligand PDB files, search space data files, molecular force field parameter files, energy minimization parameter files, constraint files and other parameters. HADDOCK uses a constrained molecular dynamics simulation algorithm to search for the most likely complex conformation by evaluating the HADDOCK score for each conformation.

1. Analyze and select results: Analyze calculation results to select complex structures with stability and biological significance. Differences between different conformations can be inspected and compared through various visualization tools, such as PyMol, Chimera, etc.

These steps are only general guidance, and the specific use method must be followed according to the specific operation manual of the software. At the same time, different software has its own special parameter settings and operating methods, and you need to understand its principles and methods to use it better.

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PRODIGY (PROtein binDIng enerGY prediction) is a web application to predict the binding affinity of protein-protein complexes based on intermolecular contacts.

Input

The protein-protein complex

PRODIGY server takes as input the three-dimensional structure of the protein-protein complex in PDB or mmCIF format:

You can choose one of the following options:

-	upload the 3D structure coordinates in PDB or mmCIF format
-	provide a protein databank ID code for automatic retrieval from the Protein Data Bank
-	Upload a multi-model PDB ensemble or .zip file with multiple structures to analyzing multiple structures at the same time (i.e. models derived from docking simulations)

Specify the chains

The user is required to specify the chain identifiers for the molecules involved in the interaction.
Interacting molecules associated with multiple chain IDs should be provided as comma-separated list.
For the FAB/HIV-1 capsid protein p24 complex (PDB code 1E6J) the input would be expected in following format:

Interactor 1: P

Interactor 2: L,H

In this example, the binding affinity will be predicted for the interface made between chain P (p24) and chains L and H (FAB).

Please note! PRODIGY only supports the 20 standard amino acids

Archive file

When submitting an archive file to PRODIGY, make sure that the chain IDs of ALL structures are compatible with the Interactors specified in the submission form.

Parameters (optional)

Temperature (in ℃)

By default the value of the dissociation constant (Kd) is calculated at 25 ℃. The user can change this value to any desired temperature.

Job ID

The user can specify a personalized Job ID to identify the run.

Email

If an email is provided, a link with the results will be sent when the job is done. The results will be stored for 2 weeks.

Output

PRODIGY outputs are displayed online and remain downloadable for 14 days. A link to the online resource is also emailed to the user, if an email is provided.

The results returned by the server include:

1.	Predicted value of the binding affinity (ΔG) expressed in kcal mol-1
2.	Calculated value of the dissociation constant (Kd) at a given temperature (25 ℃ by default), expressed in Molar (M)
3.	Number of intermolecular contacts (ICs) at the interface within the threshold distance of 5.5 Å, separately listed according to the contact property
4.	Percentage of the charged and apolar non-interacting surface (NIS%) of the complex
5.	Downloadable table (.txt) listing the residues in contact within the given threshold
6.	Downloadable ready-to-run Pymol (Delano Scientific, 2002) script (.pml) with different color coding for the interacting residues
7.	Archive file including all the output files

How to run PRODIGY locally

In case you have many structures on which you wish to run PRODIGY, we distribute the standalone version in form of a Github repository.
The link to the repository can be found at the BonvinLab software page.