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 20 CH HVY P 20 17.244 18.241 50.736 2.00 0.20 C
ATOM 20 ND DON P 20 17.244 18.241 50.736 1.00 0.58 N
ATOM 18 CH HVY P 18 18.452 17.752 51.268 2.00 0.20 C
ATOM 18 CA ARO P 18 18.452 17.752 51.268 0.70 0.28 C
ATOM 21 CH HVY P 21 16.957 19.505 50.313 2.00 0.20 C
ATOM 22 CH HVY P 22 15.713 19.683 49.527 2.00 0.20 C
ATOM 22 CA ARO P 22 15.713 19.683 49.527 0.70 0.28 C
ATOM 36 CH HVY P 36 17.643 20.506 50.528 2.00 0.20 C
ATOM 36 OA ACC P 36 17.643 20.506 50.528 1.00 0.56 O
ATOM 14 CH HVY P 14 20.800 18.082 51.969 2.00 0.20 C
ATOM 14 CA ARO P 14 20.800 18.082 51.969 0.70 0.28 C
ATOM 13 CH HVY P 13 21.893 18.937 52.110 2.00 0.20 C
ATOM 13 ND DON P 13 21.893 18.937 52.110 1.00 0.35 N
ATOM 15 CH HVY P 15 20.895 16.683 52.364 2.00 0.20 C
ATOM 15 CA ARO P 15 20.895 16.683 52.364 0.70 0.28 C
ATOM 37 CH HVY P 37 22.181 16.074 52.953 2.00 0.20 C
ATOM 16 CH HVY P 16 19.741 15.840 52.195 2.00 0.20 C
ATOM 16 CA ARO P 16 19.741 15.840 52.195 0.70 0.36 C
ATOM 17 CH HVY P 17 18.520 16.379 51.645 2.00 0.20 C
ATOM 17 CA ARO P 17 18.520 16.379 51.645 0.70 0.28 C
ATOM 19 CH HVY P 19 19.616 18.588 51.441 2.00 0.20 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(using opencadd,)
rdkit2pdbqt -l lig.sdf
rdkit2pdbqt -r rec.pdb
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:
-r [ --receptor ] arg rigid part of the receptor (PDBQT)
--flex arg flexible part of the receptor (pdbqt)
--template arg template ph4 (pdb)
-w [ --water ] arg water file (O coordicates file with
resname HOH, energy in the beta column)
--pharma arg pharmacophore[ph4] constrained file
-l [ --ligand ] arg ligand.pdbqt(ligand file, PDBQT)
--ligands_dir arg directory for ligands
--multiligs_pdbqt arg pdbqt file containing multi ligands
Search space (required):
--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)
--size_y arg size in the Y dimension (Angstroms)
--size_z arg size in the Z dimension (Angstroms)
Output (optional):
-o [ --out ] arg output models (PDBQT), the default is
chosen based on the ligand file name
--out_dir arg (=WVOUTDIR) output directory for batch mode
--score_cutoff arg (=3.40e+38) the cutoff score for output
--ph4_cutoff arg (=1.175e-38) the cutoff of ph4 for output
--log arg optionally, write log file
--genph4 generate pseudo pharmacophore model in
pdb format
Advanced options (see the manual):
--score_only score only - search space can be
omitted
--local_only do local search only
--implicitsol implicit solvation model result in a
implicitsol.pdb
--grid_space arg (=0.375) grid space
--weight_vdw arg (=0.184) vdw weight
--weight_hbond arg (=1) Hydrogen bond weight
--weight_electrop arg (=0.25) polar repulsion or hydrophobic
attraction
--weight_desol arg (=-0.5) desolvation weight[depends on water
model used]
--wclash_dist arg (=0.5) clash distance with water[depends on
water model used]
--weight_torsion arg (=0.30) external torsion weight[depends on
forcefield or unit in kj/mol or
kcal/mol]
--relax_only do relax only without BFGS refinement
for local searching
--local_steps arg (=2000) local relax steps
--tramplitude arg (=1) amplitude for translation/rotation in
local relax
--toramplitude arg (=1) amplitude for torsion in local relax
Misc (optional):
--cpu arg the number of CPUs to use (the default
is to try to detect the number of CPUs
or, failing that, use 1)
--seed arg explicit random seed
--exhaustiveness arg (=8) exhaustiveness of the global search
(roughly proportional to time): 1+
--population arg (=8) population size for genetic algorithm
--ga_search arg (=4) amplitude for ga searching loop size:
0, 1, 2...
--num_modes arg (=10) maximum number of binding modes to
generate
--rmsd arg (=1.5) modes clustering cutoff
--energy_range arg (=3) maximum energy difference between the
best binding mode and the worst one
displayed (kcal/mol)
Configuration file (optional):
-c [ --config ] arg the above options can be put here
Information (optional):
--help display usage summary
--help_advanced display usage summary with advanced
options
--verbosity arg display IO information
--version display program version