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Molecular Docking

This category contains nodes involved in molecular docking with AutoDock Vina. See the Pipeline Documentation for more details.

AutoDock Vina

This powerful tool performs molecular docking, a computational method used to predict how a small molecule (ligand) binds to a larger molecule (protein or receptor). It simulates the process of molecular recognition, searching for the most favorable orientations and positions of the ligand in a protein.

Important Note: This tool is generally not suitable for "metalloproteins" (proteins that contain metal ions as part of their structure), as it may lead to inaccurate results.

After the simulation, the node will display the top three best binding results directly. It also generates a comprehensive file containing all predicted binding conformations of the ligand, which can be further explored using the View Vina Conformations, Select Vina Conformation, or Add SDF to PDB nodes for detailed visualization of ligand-protein interactions.

References:

Eberhardt, J., Santos-Martins, D., Tillack, A. F., & Forli, S. (2021). AutoDock Vina 1.2.0: New Docking Methods, Expanded Force Field, and Python Bindings. Journal of Chemical Information and Modeling.https://doi.org/10.1021/acs.jcim.1c00203 O'Boyle, N. M., Banck, M., James, C. A., Morley, C., Vandermeersch, T., & Hutchison, G. R. (2011). Open Babel: An Open Chemical Toolbox. Journal of Cheminformatics, 3, 33.https://doi.org/10.1186/1758-2946-3-33 Trott, O., & Olson, A. J. (2010). AutoDock Vina: Improving the Speed and Accuracy of Docking with a New Scoring Function, Efficient Optimization, and Multithreading. Journal of Computational Chemistry, 31(2), 455–461.https://doi.org/10.1002/jcc.21334

Input

  • Prepared Vina Receptor Files: This input comes from the "Prepare Protein for AutoDock Vina" node. It includes the protein structure (rigid PDBQT), potentially a flexible part (flexible PDBQT), and a JSON file containing essential information about the receptor.
  • Prepared Vina Ligand Files: This input comes from the "Prepare Ligand for AutoDock Vina" node. It is a list containing the prepared PDBQT file(s) for your ligand, which may include both non-hydrated and hydrated versions depending on your previous settings.
  • AutoGrid Map Files: (Optional) This input is a list of grid map files generated by the "Map Generation with AutoGrid4" node. It is only required if you intend to perform "hydrated docking," which considers the role of water molecules in the binding process. _ Grid Parameter File (GPF): This file contains the precise coordinates and dimensions of the 3D grid box, defining the search space for the ligand around the protein. It is typically generated during the receptor preparation step.

Input Parameters

  • Exhaustiveness: An integer value that controls the computational effort AutoDock Vina spends searching for binding poses. Higher values (e.g., 32 or 64) lead to a more thorough search and generally more consistent and accurate results, but require more computation time. Lower values (e.g., 8) are faster but might miss optimal binding modes. (Range: 1 to 512, Default: 8)
  • Target Number of Conformations: An integer value specifying how many different binding poses (conformations) of the ligand you want AutoDock Vina to report. While you request a number, it's important to note that the tool might not always reach this exact number if fewer distinct poses are found. (Range: 3 to 200, Default: 5)
  • Output File Name: A text field to define the base name for all the files generated by this docking simulation. If left empty, a name will be automatically created based on the input receptor and ligand names.

Expert Parameters (available via the menu icon in the node)

This node provides access to advanced parameters for both AutoDock Vina and OpenBabel, offering fine-tuned control over the docking simulation and subsequent file processing.

AutoDock Vina Parameters:

  • --scoring: Selects the scoring function used to evaluate how well a ligand binds. Options include:
    • ad4: Based on AutoDock4's scoring function, often recommended for hydrated docking.
    • vina: AutoDock Vina's default scoring function.
    • vinardo: An alternative scoring function designed for improved accuracy.
  • --maps: Specifies the affinity maps to use. These maps are pre-calculated grid representations of the protein's environment and are essential if you use the ad4 or vina scoring functions directly (e.g., for hydrated docking).
  • -- center_x, --center_y, --center_z: Manually set the X, Y, and Z coordinates (in Angstroms) for the center of the docking grid box. These values override any automatically determined center.
  • --size_x, --size_y, --size_z: Manually set the dimensions (size in Angstroms) of the docking grid box along the X, Y, and Z axes. These values override any automatically determined box size.
  • --autobox: If enabled, AutoDock Vina will automatically determine the size and center of the docking grid box based on the input ligand's dimensions. This is commonly used for re-docking experiments.
  • --seed: Provides a specific number (seed) to initialize the random number generator used in the docking algorithm. Using the same seed will produce identical results for repetitive runs, which can be useful for reproducibility.
  • Re-dock gridbox Scaling Factor: This factor is used to scale the size of the grid box when performing re-docking experiments using the LaBOX tool (an internal utility for defining grid boxes around ligands). (Default: 3.0)

OpenBabel Parameters (used internally for output formatting):
These parameters allow minor adjustments to the output SDF files for the top 3 conformations.

  • --canonical: Ensures that the atom order within the molecule is standardized (canonicalized).
  • -d: Deletes all hydrogen atoms from the molecule, making them "implicit" (not explicitly represented).
  • --delete: Deletes specified properties from the molecule. Provide property names as a space-separated list.
  • -e: Instructs OpenBabel to continue processing molecules even if errors are encountered.
  • --errorlevel: Controls the verbosity of error and warning messages displayed (1 to 5).
  • -r: Removes all disconnected fragments from a molecule, keeping only the largest contiguous part (useful for stripping salts).
  • --title: Adds or replaces the main title of the molecule.
  • --add: Adds properties (e.g., 'MW', 'logP') to the molecule's data.
  • --addfilename: Appends the input filename to the molecule's title.
  • --addinindex: Appends the input index of the molecule to its title.
  • --addoutindex: Appends the output index of the molecule to its title.
  • --addtotitle: Appends custom text to the end of each molecule's title.
  • --append: Appends values of specific properties or descriptors to the molecule's title.
  • -b: Converts "dative bonds" to standard covalent bonds.

Output

  • Docking Conformation 1: An SDF file representing the ligand's predicted binding pose with the highest affinity (most favorable binding).
  • kcal/mol | Binding Energy for Conformation 1: The calculated binding energy (in kilocalories per mole, kcal/mol) for the highest affinity conformation. A more negative value indicates stronger binding.
  • Docking Conformation 2: An SDF file for the ligand's second highest affinity binding conformation.
  • kcal/mol | Binding Energy for Conformation 2: The calculated binding energy for the second highest affinity conformation.
  • Docking Conformation 3: An SDF file for the ligand's third highest affinity binding conformation.
  • kcal/mol | Binding Energy for Conformation 3: The calculated binding energy for the third highest affinity conformation.
  • All Ligand Conformations: A PDBQT file containing all the ligand conformations predicted by the simulation. This file is useful for detailed analysis and visualization of all possible binding poses.
  • All Docking Metrics: A CSV (Comma Separated Values) file containing a table of all predicted binding affinities and RMSD (Root Mean Square Deviation) values for each conformation generated during the docking simulation. This provides a comprehensive overview of the results.

Map Generation with AutoGrid4

Before a small molecule (ligand) can be "docked" into a protein (receptor) to predict how they might bind, we need to prepare a 3D "map" around the protein. This map describes the protein's environment, showing where different types of atoms or chemical properties would be most favourable for interaction.

This node uses a specialized tool called AutoGrid4 to create these essential "affinity maps." It takes a setup file (called a Grid Parameter File, or GPF) that defines the precise region around the protein to be mapped. The output includes several grid map files (one for each atom type or interaction), which other molecular docking tools, like AutoDock Vina, then use to efficiently calculate how well a ligand might fit and bind. It also generates a log file summarizing the mapping process. Optionally, it can also create a "water map" if your GPF is configured to include the effect of water molecules in the binding site.

References:

Forli, S., & Olson, A. J. (2012). A force field with discrete displaceable waters and desolvation entropy for hydrated ligand docking. Journal of Medicinal Chemistry, 55(2), 623–638.https://doi.org/10.1021/jm2005145

Input

  • Prepared Vina Receptor Files: This input typically comes from a "Prepare Protein" node. It includes the 3D structure of your protein in a special format (PDBQT files) and any associated supporting information.
  • Grid Parameter File (GPF): A text file (.gpf) that contains all the settings for AutoGrid4, such as the dimensions and location of the 3D grid, and which atom types to calculate affinities for. This file is usually generated during the initial protein preparation steps.

Input Parameters

  • Generate Water Map Files: If set to 'on', AutoGrid4 will also generate an additional map file specifically accounting for the potential presence of water molecules in the binding site. This can sometimes improve the accuracy of docking predictions for certain systems. (Default: Off)

Output

  • AutoGrid Map Files: A ZIP-file of generated 3D grid files (.map files). Each file in this ZIP-file represents a different type of interaction or atom affinity within the grid. These maps are crucial inputs for subsequent molecular docking simulations.
  • Output GLG: The Grid Log File (.glg). This file contains a detailed record of the AutoGrid4 process, including messages about its progress, any warnings, and confirmation of successful completion. It can be useful for troubleshooting or verifying that the mapping process ran as expected.

Prepare Ligand for AutoDock Vina

This tool is used to prepare small molecules, often called "ligands," for molecular docking simulations with AutoDock Vina. Its primary function is to convert ligand structure files (SDF) into the specific PDBQT format that AutoDock Vina requires. The PDBQT format includes not only the 3D atomic coordinates but also crucial information such as atom types and partial atomic charges, which are essential for accurate docking calculations.

The preparation process involves assigning proper atom types and charges. This node can also optionally add explicit water molecules to the ligand's structure, which is useful for "hydrated docking" simulations where water molecules in the binding site play an important role.

Reference:

Forli, S., & The Forli Laboratory. (2025). Meeko: interface for AutoDock (version 0.6.1). Retrieved from https://github.com/forlilab/Meeko

Input

  • Input Ligand: The file containing the 3D structure of your small molecule (ligand) in SDF format.

Input Parameters

  • Hydrate Ligand: If enabled, the tool will add explicit water molecules to the ligand structure. This is used when performing docking simulations that explicitly account for the presence and interaction of water molecules within the binding site. (Default: Off)
  • Output Filename: A text field to specify the name of the output PDBQT file(s). If left empty, a name will be automatically generated, typically by appending "_prepared" to the original input file name.

Expert Parameters (available via the menu icon in the node)

This node provides advanced parameters for the Meeko ligand preparation tool, allowing for fine-tuned control over how your ligand is processed.

  • Charge Model: This parameter determines how partial electrical charges are assigned to the atoms in your ligand. Accurate partial charges are crucial for correctly calculating electrostatic interactions during docking. Options include 'gasteiger' (a common empirical method), 'espaloma', or 'zero' (no charges). (Default: 'gasteiger')
  • Keep Macrocycles Rigid: If enabled, this option will prevent large ring structures (macrocycles) within your ligand from being treated as flexible during the preparation, meaning their internal conformation will be maintained as in the input file.
  • Remove SMILES: If enabled, the SMILES string (a textual representation of the molecule's structure) will not be included as a remark in the generated PDBQT output file.
  • Keep Chorded Rings: This relates to how the tool identifies and processes ring systems in the molecule. If enabled, it retains certain types of ring perceptions that might otherwise be simplified.
  • Keep Equivalent Rings: Similar to Keep Chorded Rings, this option influences how redundant or equivalent ring structures are treated during analysis.
  • Minimum Ring Size: This parameter is intended to define the smallest number of atoms a ring must have to be considered for certain processing steps, such as ring opening during flexibility analysis.
  • Hydrate: This parameter is explicitly for adding water molecules to the ligand structure. (Note: This might be redundant with the main "Hydrate Ligand" input parameter; if both are present, the behavior should be confirmed by testing).
  • Merge Atom Types: This option allows you to specify a list of atom types (e.g., 'H' for hydrogen) that should be merged or treated equivalently during the PDBQT conversion. The default is usually to merge hydrogens.
  • Rigidify Bonds SMARTS: If enabled, you can provide SMARTS patterns (a chemical language for defining substructures) to force specific bonds identified by that pattern to be treated as rigid (non-rotatable) in the ligand.
  • Rigidify Bonds Indices: If enabled, you can specify the numerical indices of two atoms that form a bond you wish to make rigid. Atom indices typically start from 1.
  • Allow rotatable amide bonds: By default, amide bonds (a common linkage in proteins and some ligands) are treated as planar and non-rotatable. If enabled, this option allows them to rotate, which is generally not recommended as it can lead to unrealistic conformations.
  • Allow bad charge: If enabled, the tool will permit outputting PDBQT files even if the calculated atomic charges are problematic (e.g., Not a Number (NaN) or Infinity (Inf)). This is strongly not recommended, as it can lead to severe errors in downstream docking simulations.

Output

  • Prepared Vina Ligand Files: A list containing one or two PDBQT files for your ligand, ready to be used as input for AutoDock Vina simulations:
    • The primary PDBQT file for your ligand, without explicit water molecules.
    • If "Hydrate Ligand" was enabled, an additional PDBQT file for your ligand that includes explicit water molecules.

Prepare Protein for AutoDock Vina

This tool is designed to get your protein structure ready for molecular docking simulations using AutoDock Vina. It uses the Meeko library to perform several crucial preparation steps. It converts the protein into a specialized file format called PDBQT, which AutoDock Vina understands. It also generates a vital JSON file that contains information needed for later analysis of the docking results.

A key feature of this tool is defining the "grid box," which is the 3D space around your protein where the docking simulation will occur. You can either let the tool automatically calculate this box based on your protein or a specific ligand (useful for "re-docking" a known ligand). Additionally, if your protein has parts that are known to be flexible and important for binding, you can specify these "flexible residues," allowing them to move and adapt during the docking simulation, potentially leading to more accurate predictions.

Reference:

Forli, S., & The Forli Laboratory. (2025). Meeko: interface for AutoDock (version 0.6.1). Retrieved from https://github.com/forlilab/Meeko

Input

  • Receptor PDB: The 3D structure of your target protein, provided as a PDB file (.pdb). This is the protein you want to dock ligands into.
  • Prepared Vina Ligand Files: : A list of PDBQT files for your ligand(s). This input is specifically used if you enable the "Gridbox from Ligand (Re-docking)" option, as it helps determine the optimal size and position of the docking grid.

Input Parameters

  • Flexible Residues: A text field where you can specify amino acid residues (the building blocks of proteins) that should be treated as flexible during the docking simulation. This is defined by the protein chain ID and residue number, for example, "A:5,7,B:12" would make residue 5 and 7 on chain A, and residue 12 on chain B, flexible. If left empty, the entire protein will be treated as rigid.
  • Gridbox from Ligand (Re-docking): If enabled, the docking grid box (the 3D area where the ligand will search for binding sites) will be automatically calculated based on the dimensions and position of the input ligand. This is particularly useful when you are "re-docking" a ligand back into a known binding site on a protein. If disabled, the grid box is calculated based on the entire receptor protein.
  • Output Filename: A text field to specify the base name for all output files generated by this node. If left empty, a name will be automatically generated, typically based on the input protein file.

Expert Parameters (available via the menu icon in the node)

This node provides access to advanced parameters for the Meeko preparation tool, allowing for more specific control over the protein preparation and grid box definition.

  • Delete Residues: Allows you to specify and remove specific residues from the protein structure before preparation. This can be useful for removing unwanted parts of the protein, such as tags or loosely bound solvent molecules. Provide residue specifications like "A:350,B:15,16,17".
  • Allow Bad Residues: If enabled, the tool will ignore residues that have missing atoms rather than stopping the process with an error. Use this with caution, as ignoring missing atoms might affect the quality of your docking results.
  • Gridbox Center: Allows you to manually define the X, Y, and Z coordinates (in Angstroms) for the center of your docking grid box. Values should be separated by commas (e.g., "10.0, -5.0, 20.0"). This overrides any automatic grid box calculation.
  • Gridbox Dimensions: Allows you to manually define the X, Y, and Z dimensions (in Angstroms) of your docking grid box. Values should be separated by commas (e.g., "60, 60, 60"). This overrides any automatic grid box calculation.

Output

  • Prepared Vina Receptor Files: A list of files containing the processed receptor data essential for AutoDock Vina. This includes:
    • A PDBQT file for the "rigid" (non-moving) part of your protein.
    • A PDBQT file for the "flexible" part of your protein (if flexible residues were specified).
    • A JSON file containing important metadata and mapping information needed by AutoDock Vina for subsequent analysis steps.
  • Grid Parameter File (GPF): A text file (.gpf) that specifies all the parameters for the docking grid, including its center and dimensions. This file is directly used by the "Map Generation with AutoGrid4" node to create the affinity maps.

Select Flexible Receptor Conformation

This tool helps you examine and extract specific receptor conformations from molecular docking simulations performed with AutoDock Vina, especially when flexible residues were defined during the protein preparation. After a docking run, particularly one involving flexible receptor components, AutoDock Vina (via the "View Vina Conformations" node) generates a multi-MODEL PDB file where each model represents a predicted ligand binding pose, and the flexible parts of the receptor are also updated for each pose. This node allows you to select one of these predicted receptor conformations (corresponding to a specific ligand pose) and save it as a separate PDB file for further analysis or visualization. This is particularly useful for focusing on the receptor's induced fit or conformational changes in response to ligand binding.

Input

  • Merged Protein-Ligand 3D File: The input PDB file (.pdb) that contains the multi-MODEL conformations of the ligand with the receptor. This file is generated by the View Vina Conformations node.

Input Parameters

  • Receptor Model Number: An integer that specifies which particular receptor conformation (model) you want to extract from the input multi-MODEL PDB file. AutoDock Vina typically ranks its predictions, with Model 1 usually being the most favorable (lowest binding energy). You would input '1' to select the top-ranked model, '2' for the second-ranked, and so on. The numbering starts from 1. (Default: 1)
  • Output File Name: A text field to specify the name of the new file that will contain only the chosen receptor conformation. The output file will be saved in PDB format. If you leave this field empty, a descriptive name will be generated automatically based on the input file and the selected model number.

Output

  • Receptor Structure File: A PDB file containing the 3D coordinates and structural information of the single, chosen receptor conformation. This file can be used with molecular visualization software to inspect the receptor's conformation corresponding to a specific ligand binding pose, or as input for other downstream analysis tools like GROMACS or docking etc.

Select Vina Conformation

This tool helps you examine and extract specific results from molecular docking simulations performed with AutoDock Vina. After a docking run, AutoDock Vina generates a file containing multiple possible ways (conformations) a small molecule (ligand) could bind to a protein. This node allows you to select one of these predicted binding poses and save it as a separate file for further analysis or visualization. This is particularly useful for focusing on the most promising binding pose or comparing different poses.

Reference:

O'Boyle, N. M., Banck, M., James, C. A., Morley, C., Vandermeersch, T., & Hutchison, G. R. (2011). Open Babel: An Open Chemical Toolbox. Journal of Cheminformatics, 3, 33.https://doi.org/10.1186/1758-2946-3-33

Input

  • All Ligand Conformations: This is the output file (in PDBQT format) directly generated by the AutoDock Vina tool. It contains a collection of all the different predicted binding poses (conformations) of your ligand within the protein's binding site, along with their associated binding energies.

Input Parameters

  • Model Number: An integer that specifies which particular binding pose (conformation) you want to extract from the AutoDock Vina output. AutoDock Vina typically ranks its predictions, with Model 1 usually being the most favorable (lowest binding energy). You would input '1' to select the top-ranked model, '2' for the second-ranked, and so on. The numbering starts from 1. (Default: 1)
  • Output File Name: A text field to specify the name of the new file that will contain only the chosen conformation. The output file will be saved in SDF format. If you leave this field empty, a descriptive name will be generated automatically based on the input file and the selected model number.

Output

  • Ligand Structure File: An SDF (Structure-Data File) file containing the 3D coordinates and structural information of the single, chosen ligand conformation. This file can be used with molecular visualization software to inspect the binding pose or as input for other downstream analysis tools.

View Vina Conformations

This tool helps you visualize the results of your molecular docking simulations performed with AutoDock Vina. After docking, Vina generates a file containing multiple possible ways (conformations) your small molecule (ligand) could bind to the protein. This node takes these results and creates a single "movie-like" PDB file that shows each predicted ligand binding pose alongside the protein receptor. If your docking simulation involved flexible parts of the protein, this tool will also correctly update their positions for each ligand pose. The resulting file is ideal for viewing in molecular visualization software like Mol* to analyze the different binding modes.

Additionally, for advanced hydrated docking simulations, this node can process the results to score the contributions of water molecules involved in the ligand-protein interactions.

Reference:

Forli, S., & The Forli Laboratory. (2025). Meeko: interface for AutoDock (version 0.6.1). Retrieved from https://github.com/forlilab/Meeko

Input

  • Prepared Vina Receptor Files: This input typically comes from the Prepare Protein for AutoDock Vina node. It includes the rigid and flexible PDBQT files of your receptor and a crucial JSON file that contains mapping information necessary for accurately processing the docking results.
  • All Ligand Conformations: The PDBQT file output directly from the AutoDock Vina docking process. This file contains all the predicted binding poses (conformations) of your ligand.

Input Parameters

  • Score Hydrated Docking Results: If enabled, the tool will analyze the contribution of water molecules to the docking results using a specialized script (dry.py). This option requires a "Water Map File" from the AutoGrid4 mapping step. (Default: Off)
  • AutoGrid Map Files: A list of grid map files generated by the Map Generation with AutoGrid4 node. This input is only required if you enable "Score Hydrated Docking Results", as it provides the water map needed for the analysis.
  • Output File Name: A text field to specify the name of the combined multi-MODEL PDB file. If left empty, a descriptive name will be automatically generated.

Output

  • Merged Protein Ligand Movie: A multi-MODEL PDB file (.pdb). This file contains the receptor structure, and for each predicted ligand pose, it includes the ligand's coordinates placed within the receptor. If flexible residues were defined in the receptor preparation, their positions will also be updated for each pose. This single file can be loaded into molecular visualization software to play an animation or sequentially view all predicted binding conformations. If "Score Hydrated Docking Results" was enabled, the first model in the movie will also include the scored conserved water molecules.