Flare Docking

Options

Basic

Column containing the ligands to dock

The column in the first input data table containing the molecules to be docked.

Optional: Column containing the ligand to define the docking grid

The column in the second input data table containing an optional ligand to define the docking grid, in the appropriate 3D conformation.

Optional: column containing a template ligand

The column in the third input data table containing an optional template ligand, in the appropriate 3D conformation. In template docking the molecules to be docked are aligned by substructure to the template ligand, and the aligned conformation is used to seed the docking run, generally leading to improved docking results for congeneric ligand series. This option is not available for covalent docking.

Column containing the protein to dock into

The column in the fourth input data table containing the prepared protein structure to use for docking. Note that all chains in the protein will be included in the docking experiment: any unwanted chains (e.g. ligands, water) must be deleted. You can use Flare to prepare your protein and delete any unwanted chains.

Calculation method

The available docking methods are briefly described below.

• Quick: uses the virtual screening docking algorithm, faster but slightly less precise. Recommended for screening of larger libraries where processing speed is very important
• Normal: the default docking algorithm
• Accurate but Slow: default docking algorithm, performing 3 independent docking runs
• Very Accurate but Slow: uses the extra-precision docking algorithm to increase accuracy and reliability of predictions, and performs 3 independent docking runs
• Score Only: calculated Delta G and VS scores for the ligands, allowing optimization of the poses

Grid definition

Every docking experiment begins with the computation of energy maps for the site of interest in a protein structure (the 'energy grid box'), where the ligand(s) are expected to dock. The dimensions of the energy grid box set the boundaries of the search space for docking a ligand. In most cases, energy grids are built around a protein's putative active site. Choosing the correct position and dimensions of the energy grid box is critically important to docking experiments, as the amount of computations in search of the optimal docked poses increases in proportion to the volume of the energy grid box. In Flare Docking, three methods are available for defining the energy grid box:

• Specify grid coordinates: define the energy grid box by mapping 2 opposite vertices of the grid box in the format min_x,min_y,min_z,max_x,max_y,max_z, for example: -3,-6.2,2,12,8.6,5. A quick method to find the appropriate grid values to use is to open the protein structure in Flare and pick the atoms which define the grid. Then in the Python Console run these commands which will print the grid values:
  grid = flare.atom_pick.corners(flare.main_window().picked_atoms)
  print(f'{grid[0][0]},{grid[0][1]},{grid[0][2]},{grid[1][0]},{grid[1][1]},{grid[1][2]}')
• Use a ligand: the ligands will be docked in the region specified by this ligand, expanded to include the protein atoms within 6Å
• Use grid data: use a pre-calculated energy grid imported with the protein.

Note that if the input protein already has an associated energy grid, this will not be recalculated.

Choose the covalent residue

Covalent docking in Flare supports the binding to the nucleophilic residues Cysteine, Lysine, Tyrosine, Threonine and Serine. Specify the name of the residue in the active site of the protein that the ligands should be covalently docked to, e.g. A LYS 745. The name for a residue you wish to use for covalent docking can be found in the tooltip when hovering over the residue in the Flare GUI.

Advanced

Quality

Define the quality of the docking algorithm to use:

• Virtual Screening: uses a faster but slightly less precise docking algorithm. Recommended for screening of larger ligand libraries where processing speed is very important
• Normal: the default docking algorithm
• Extra Precision: uses the most rigorous sampling and scoring algorithms to increase accuracy and reliability of predictions at the cost of slower speed of processing
• Score Only - Allow Pose Optimization: calculates Delta G and VS scores for the ligands, allowing optimization of the poses
• Score Only - Keep Pose Fixed: calculates Delta G and VS scores for the ligands in a fixed position.

Max Poses

The max number of poses to output for each ligand (default: 10)

Pool Size

Fine tune the Lead Finder genetic algorithm parameters: increase the number of individuals in the initial pool by the given factor.

Population Size

Fine tune the Lead Finder genetic algorithm parameters: increase the number of individuals in a population by the given factor.

Minimize ligands before docking

If checked, the ligands to dock will be popped to 3D if required and minimized before starting the docking run, as Lead Finder only samples and minimizes in torsional space.

Rotate Amide Bonds

Rotate amide bonds during docking. If not set then amides will be forced to the trans conformation.

Rotate Ester Bonds

Rotate ester bonds (O=)C-O(-C) during docking. If not set then esters will be kept in the input conformation.

Number of runs

The number of independent docking runs to perform.

Add column containing log

If checked, the log of the docking process for each molecule is added as a column 'FlareDocking_Log'.

Docking constraints

Constraints for docking. This should be a residue name, an atom name, a type, and an associated strength. The type can be 'h' for hydrogen bonding, 'm' for metal, 's' for salt bridge, 'p' for pi-pi, or 'c' for cation-pi. The constraint strength can be weak (w), normal (n) or strong (s). As the residue name contains spaces it should be surrounded with quotation marks. Multiple constraints can be specified by using multiple of lines.
Example:

"A LEU 10" H h w
"A LYS 12" NZ c s

Maximum Docking Constraint Penalty

Set the maximum docking constraint penalty that will be tolerated. With the default value of 1.0, docking poses that do not match the provided docking constraints will be discarded. To let Lead Finder produce poses that violate the constraints, set this to a high value (e.g. 100).

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• Error: module ‘rdkit.Chem’ has no attribute ‘Mol’by eneas77 on 2023-07-10

  forum.knime.com/p/228371

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