dockingvina
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dockingvina [2012/10/13 17:47] – [Results] sanmark | dockingvina [2012/12/17 21:35] – rkiss | ||
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====== Docking (Vina) ====== | ====== Docking (Vina) ====== | ||
+ | {{: | ||
Molecular docking is a method that predicts the binding orientation of one small molecule at the binding site of a target macromolecule (protein, DNA, carbohydrates, | Molecular docking is a method that predicts the binding orientation of one small molecule at the binding site of a target macromolecule (protein, DNA, carbohydrates, | ||
- | The Docking (Vina) workflow step utilizes the Vina docking algorithm | + | The Docking (Vina) workflow step utilizes the [[http:// |
===== When to use ===== | ===== When to use ===== | ||
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Docking plays a critical role in structure-based drug design projects, where the binding affinity of thousands or even millions of compounds should be assessed to identify potent inhibitors or activators of therapeutically relevant macromolecules, | Docking plays a critical role in structure-based drug design projects, where the binding affinity of thousands or even millions of compounds should be assessed to identify potent inhibitors or activators of therapeutically relevant macromolecules, | ||
- | It can identify new drug candidates (structure-based virtual screening), or help to rationalize the binding mode of known ligands. It can give ideas about how ligands can be further developed to maximize interaction with the target. Docking can be utilized when the structure of the target has been experimentally determined or a high quality model is available. | + | It can identify new drug candidates (structure-based |
===== How to use ===== | ===== How to use ===== | ||
- | If you are new to docking, it is suggested to choose one of the ~10,000 prepared target structures. If you are more experienced, | + | If you are new to docking, it is suggested to choose one of the ~10,000 prepared target structures. If you are more experienced, |
Docking results are ranked by docking scores (the more negative the better), which indicates how well the ligand is predicted to bind to the target. It is, however, also important to check the binding mode and analyze whether it is in agreement with a priori knowledge. | Docking results are ranked by docking scores (the more negative the better), which indicates how well the ligand is predicted to bind to the target. It is, however, also important to check the binding mode and analyze whether it is in agreement with a priori knowledge. | ||
- | Since docking is one of the most computationally intensive drug discovery tools, it is highly recommended to apply it in the last steps in a screening workflow. | + | Since docking is one of the most computationally intensive drug discovery tools, it is highly recommended to apply it in the last steps in a screening workflow. |
==== Options ==== | ==== Options ==== | ||
- | Nearly 10,000 automatically prepared target structures integrated from the sc-PDB database (link) (ref) are immediately for target selection. These and your previously uploaded targets are available by clicking on “Select target”. Alternatively, | + | Nearly 10,000 automatically prepared target structures integrated from the [[http:// |
- | Selecting target | + | == Selecting target |
- | When browsing the already available targets, you can search/ | + | |
- | Target visualization | + | {{: |
- | By default, protein main chains are displayed as ribbons and sidechains as lines. Heteroatoms (if any) are displayed as sticks. You can use your mouse or touchpad buttons to rotate (Left button), zoom (Right button or Scroll or Shift+Left button), translate (Middle button or Ctrl+Left button) and slab (Ctrl+Right button). For 3D visualization we use the WebGL/ | + | |
+ | When browsing the already available targets, you can search/ | ||
+ | |||
+ | == Target visualization | ||
+ | |||
+ | {{: | ||
+ | |||
+ | By default, protein main chains are displayed as ribbons and sidechains as lines. Heteroatoms (if any) are displayed as sticks. You can use your mouse or touchpad buttons to rotate (Left button), zoom (Right button or Scroll or Shift+Left button), translate (Middle button or Ctrl+Left button) and slab (Ctrl+Right button). For 3D visualization we use the WebGL/ | ||
+ | |||
+ | == Upload target == | ||
+ | |||
+ | {{: | ||
- | Upload target | ||
You can upload your own target by clicking on “Upload a file”. All uploaded files will remain private and won't be accessible by any other user. | You can upload your own target by clicking on “Upload a file”. All uploaded files will remain private and won't be accessible by any other user. | ||
For each uploaded file you can optionally add associated data, such as Name (name of the uploaded file by default), PDB ID, Uniprot Name, Uniprot Accession ID/ | For each uploaded file you can optionally add associated data, such as Name (name of the uploaded file by default), PDB ID, Uniprot Name, Uniprot Accession ID/ | ||
- | You can also run an automatic target preparation for docking by ticking the “Preparation” box, in which case, AutoDockTools | + | You can also run an automatic target preparation for docking by ticking the “Preparation” box, in which case, [[http:// |
- | Binding site center | + | == Binding site center |
- | X, Y and Z coordinates (from the coordinate system of the protein). These are automatically populated with values if they are present in the target database. Coordinates are available for all targets derived from the sc-PDB database | + | |
+ | X, Y and Z coordinates (from the coordinate system of the protein). These are automatically populated with values if they are present in the target database. Coordinates are available for all targets derived from the [[http:// | ||
+ | |||
+ | == Binding site area == | ||
- | Binding site area | ||
Size of the binding size in Angstroms. Default value is 22, which typically covers a sufficiently large space for docking typical small molecules. | Size of the binding size in Angstroms. Default value is 22, which typically covers a sufficiently large space for docking typical small molecules. | ||
- | Maximum number of binding modes / ligand | + | == Maximum number of binding modes / ligand |
Number of binding poses to be saved per ligand (default: 1, max: 9) | Number of binding poses to be saved per ligand (default: 1, max: 9) | ||
- | Exhaustiveness | + | == Exhaustiveness |
This parameter sets the exhaustiveness of conformational sampling of docking (default: 2, max: 8). We found that a value of “2” is typically sufficient for the conformational sampling of small molecules. | This parameter sets the exhaustiveness of conformational sampling of docking (default: 2, max: 8). We found that a value of “2” is typically sufficient for the conformational sampling of small molecules. | ||
===== Results ===== | ===== Results ===== | ||
- | | + | {{: |
- | * Docking (Vina) score (displayed as a single column in both List(link) | + | |
- | * hits will be ordered by the Docking (Vina) score | + | |
- | * docking | + | * Docking (Vina) score (displayed as a single column in both List and Table views): the docking score of Vina is a (very rough) estimation of the binding affinity (free energy of binding). More negative docking scores suggest higher affinity. |
+ | * Hits will be ordered by the Docking (Vina) score | ||
+ | * Docking | ||
===== Limits ===== | ===== Limits ===== | ||
- | The Docking (Vina) filter available in the Free package | + | The Docking (Vina) filter available in the [[freepackage|Free package]] is limited to 500 input molecules per month. If you need more, [[subscriptionpackages|subscribe]] to our Docking (Vina) package. |
===== Docking protocol ===== | ===== Docking protocol ===== | ||
Docking (Vina) workflow step requires input ligands with a valid 3D structure, therefore the input ligand collection is prepared for docking as follows. Unknown or undefined tetrahedral stereocenters and cis-trans double bonds are converted into well-defined centers and double bonds by the stereoisomer generator of mcule. Molecules failed to dock are skipped. To ensure that molecule conversions did not affect the identity of the molecule, InChI strings of the docking input and output are compared and in case of InChI mismatch, the molecule is skipped. | Docking (Vina) workflow step requires input ligands with a valid 3D structure, therefore the input ligand collection is prepared for docking as follows. Unknown or undefined tetrahedral stereocenters and cis-trans double bonds are converted into well-defined centers and double bonds by the stereoisomer generator of mcule. Molecules failed to dock are skipped. To ensure that molecule conversions did not affect the identity of the molecule, InChI strings of the docking input and output are compared and in case of InChI mismatch, the molecule is skipped. |
dockingvina.txt · Last modified: 2014/03/29 20:58 by flack