For drug design purpose, explicit or implicit waters, pharmacophore or position constrained docking, external torsion parameter (in amber/gaff/charmm force field like parameters) are supported in watvina.
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 --pharma a_txt_file.txt
the format of a_txt_file.txtis:
name x y z cut_off_distance weight
for example:
ACC 0.0 0.0 0.0 0.3 0.5
ACC: the hbond acceptor
0.0 0.0 0.0: the coordinate of hbond acceptor
0.3: the cut off distance is 0.3
0.5: the award weight is 0.5, finally the score is (1+0.5)*watvina_score
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 --pharma a_txt_file.txt
similar to pharmacophore constrained docking, the position constrained pharmacophore name is:
BFAX
The X is the atom serial number in the ligand pdbqt file.
for example, BFA4, the atom with serial number 4 will be fixed to a position.
2.5 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:
--receptor arg rigid part of the receptor (PDBQT)
--flex arg flexible part of the receptor (pdbqt)
--water arg water file (O coordicates file with
resname HOH, energy in the beta column)
--pharma arg pharmacophore restraints
--ligand arg ligand.pdbqt(ligand file, PDBQT)
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):
--out arg output models (PDBQT), the default is
chosen based on the ligand file name
--log arg optionally, write log file
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
--randomize_only randomize input, attempting to avoid
clashes
--weight_vdw arg (=0.193000004) vdw weight
--weight_hbond arg (=0.600000024) Hydrogen bond weight
--weight_electrop arg (=0.140000001) polar repulsion or hydrophobic
attraction
--weight_desol arg (=-1) desolvation weight[depends on water
model used]
--wclash_dist arg (=1.39999998) clash distance with water[depends on
water model used]
--weight_torsion arg (=0.300000012) external torsion weight[depends on
forcefield or unit in kj/mol or
kcal/mol]
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 (=6) exhaustiveness of the global search
(roughly proportional to time): 1+
--population arg (=3) population size for genetic algorithm
--ga_search arg (=2) amplitude for ga searching loop size
--num_modes arg (=20) 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):
--config arg the above options can be put here
Information (optional):
--help display usage summary
--help_advanced display usage summary with advanced
options
--version display program version
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