Watvina facilitates drug design with support for explicit or implicit waters, pharmacophore or position-constrained docking, and external torsion parameters (akin to amber/gaff/charmm force fields).
1.1 Receptor and ligand(s) should be carefully prepared. KEEP ALL THE NON-POLAR AND POLAR HYDROGENS.
1.3 Hydroxy hydrogens which do not formed intra hydrogen bond in the receptor are suggested to be flexible. Another method is to change the OA and HD atom types to OW and HW respectively.
Opendx format was not supported now, but later on it will be online. In addition, the desolvation weight has to be adjusted mannually due to the energy calculated from different methods.
watvina --config vina.conf --water water.pdb
In the water.pdb file with energy value (calculated from GIST, WATSite, Watermap, lesite etc) in the beta factor column. Keep the Oxygen atoms only, and with a resname HOH.
Desolvation was calculated from water probe generated energy map
watvina --config vina.conf --implicitsol
watvina --config vina.conf --template a_pseudo_pharmacophore_pdb_file.pdb
the format of a_pseudo_pharmacophore_pdb_file.pdbis in pdbformat
ATOM 1 CH HVY P 2 -0.605 29.778 21.561 2.00 0.20 C
ATOM 2 CH HVY P 12 1.270 28.887 19.820 2.00 0.20 C
ATOM 3 CH HVY P 13 2.006 27.868 19.172 2.00 0.20 C
ATOM 4 CA ARO P 13 2.006 27.868 19.172 0.70 0.27 C
ATOM 5 CH HVY P 17 2.939 28.100 18.157 2.00 0.20 C
ATOM 6 ND DON P 17 2.939 28.100 18.157 1.00 0.41 N
ATOM 7 CH HVY P 14 1.727 26.553 19.510 2.00 0.20 C
ATOM 8 CH HVY P 3 -0.477 29.435 22.941 2.00 0.20 C
ATOM 9 OA ACC P 3 -0.477 29.435 22.941 1.00 0.48 O
ATOM 10 CH HVY P 7 -3.861 31.122 17.827 2.00 0.20 C
ATOM 11 CH HVY P 18 2.859 29.108 17.251 2.00 0.20 C
ATOM 12 CH HVY P 20 2.164 30.901 16.325 2.00 0.20 C
ATOM 13 CH HVY P 23 1.204 31.967 16.050 2.00 0.20 C
ATOM 14 CA ARO P 23 1.204 31.967 16.050 0.70 0.26 C
ATOM 15 CH HVY P 21 3.350 30.513 15.703 2.00 0.20 C
ATOM 16 CA ARO P 21 3.350 30.513 15.703 0.70 0.43 C
ATOM 17 CH HVY P 22 3.811 29.380 16.306 2.00 0.20 C
ATOM 18 OA ACC P 22 3.811 29.380 16.306 1.00 0.70 O
ATOM 19 CH HVY P 24 1.152 32.577 14.797 2.00 0.20 C
ATOM 20 CA ARO P 24 1.152 32.577 14.797 0.70 0.30 C
where resname for pharmacophore type; occupancyfor cutoff distance and b-factor for contribution weight.
If only keep the HVY, the heavy atoms, the model is quite similar to a molecular shape,
while other pharmacophores for the colors in shape.
watvina can generate a initial template ph4.pdb file based on the protein and ligand interaction.
watvina --config vina.conf --score_only --genph4
other pharmacophores:
DON: hbond donor;
ARO: for aromatic carbons;
PCG: for positively charged nitroge or guanidine carbon;
NCG: for negatively charged center;
SGM: Cl, Br, I, S;
HYP: hydrophobic atoms(hydrophobic carbon, Cl, Br, I)
HVY: any heavy atoms(not hydrogen)
position constrained docking is useful for FEP, enzymatic pre-active pose prediction...
watvina --config vina.conf --tramplitude 0
--tramplitude 0 will freeze the ROOT of the ligand.
watvina --config vina.conf --toramplitude 0
--toramplitude 0 will frozen the torsions of the ligand
2.7 The pdbqt files for receptors and ligands are prepared from their pdb file by mgltools, or from rdkit2pdbqt.py
rdkit2pdbqt.py -l lig.sdf
rdkit2pdbqt.py -r rec.pdb
or setup the scaffold as ROOT of the pdbqt
rdkit2pdbqt.py -l lig.sdf core.sdf
External torsion parameters in the header of ligand file
the format is
REMARK TORSION INDEX i j k l V/2 theta_0 n
for examle:
REMARK TORSION INDEX 18 17 16 21 0.16 0 3
Input options:
-r, --receptor arg Rigid part of the receptor (PDBQT/PDB)
--flex arg Flexible part of the receptor (pdbqt)
--template arg Template ph4 (pdb)
-w, --water arg Water file (O coordinates file with resname HOH,
energy in the beta column)
--pharma arg Pharmacophore[ph4] constrained file
--ligands_dir arg Directory for ligands
--multiligs_pdbqt arg PDBQT file containing multi ligands
-l, --ligand arg Ligand.pdbqt(ligand file, PDBQT/SDF)
Output options:
-o, --out arg Output models (PDBQT/SDF)
--out_dir arg Output directory for batch mode (default: OUTDIR)
--score_cutoff arg The cutoff score for output (default: 10000)
--ph4_cutoff arg The cutoff of ph4 for output (default: -1.0)
--timeout_cutoff arg The timeout for each thread (default: 600)
--log arg Optionally, write log file
Search Space options:
--center_x arg X coordinate of the center
--center_y arg Y coordinate of the center
--center_z arg Z coordinate of the center
--size_x arg Size in the X dimension (Angstroms) (default: 25)
--size_y arg Size in the Y dimension (Angstroms) (default: 25)
--size_z arg Size in the Z dimension (Angstroms) (default: 25)
Misc options:
--cpu arg The number of CPUs to use
--seed arg Explicit random seed
--exhaustiveness arg Exhaustiveness of the global search (default: 8)
--population arg Population size for genetic algorithm (default: 8)
--ga_search arg Amplitude for ga searching loop size (default: 4)
--num_modes arg Maximum number of binding modes to generate
(default: 10)
--rmsd arg Modes clustering cutoff (default: 1.5)
--energy_range arg Maximum energy difference between the best binding
mode and the worst one displayed (kcal/mol)
(default: 3.0)
Config File options:
-c, --config arg The above options can be put here
Advanced options:
--score_only Score only - search space can be omitted
--genph4 Generate pseudo pharmacophore model in pdb format
--local_only Do local search only
--implicitsol Implicit solvation model result in an
wgrid.pdb
--grid_space arg Grid space (default: 0.375)
--weight_vdw arg Vdw weight (default: 0.184)
--weight_hbond arg Hydrogen bond weight (default: 1.000)
--weight_electrop arg Polar repulsion or hydrophobic attraction
(default: 0.250)
--weight_desol arg Desolvation weight [depends on water model used]
(default: -0.500)
--wclash_dist arg Clash distance with water [depends on water model
used] (default: 0.500)
--weight_torsion arg External torsion weight [depends on forcefield or
unit ] (default: 0.300)
--relax_only Do relax only without BFGS refinement for local
searching
--local_steps arg Local relax steps (default: 2000)
--tramplitude arg Amplitude for translation/rotation in local relax
(default: 1.000)
--toramplitude arg Amplitude for torsion in local relax (default:
1.000)
Information options:
-h, --help Display usage summary
--help_advanced Display usage summary with advanced options
--verbosity arg Display IO information (default: 2)
-v, --version Display program version