Maestro/Omega/MGLTools/Autodock Vina Method 1
Chimera (1.10.1)
OpenBabel (2.4.1)
Assumed pH 7.4
Gasteiger charges
Crystal ligands from the 20 structures released at Stage1b were extracted and saved separately using sdf format.
For each unknown ligand in free energy dataset, the most similar ligand from 20 crystal ligands were extracted.
Gradient descent 20 steps and gradient conjugate 50 steps;
The most similar ligand(template) from 20 crystal ligands released at stage 1b was identified for each unknown ligand(target) in free energy dataset. Then manually mutated the template to target and followed by a energy minimization using parameter list above. The final pose was treated as the predicted binding pose.
Yes
Yes
Laufer_Seed
MELD (0.3.10)
Chimera (1.10.1)
OpenBabel (2.4.1)
Mdtraj( 1.9.1)
Cpptraj (v17.00b)
Antechamber
Tleap
MELD distance restraint R3=0.7nm,R4=0.9nm;
MELD distance restraint enforce=50%;
REST2 solute scaling temperature range: 300-400K;
MELD replica exchange simulation time step 4.5fs;
The ligands were represented by the GAFF force field, protein was represented by
the AmberFF14SB force field and TIP3P water model was used. Replica exchange molecular dynamic
simulations were performed for system containing one recept and two different ligands in a periodic
cube box with buffer distance 10A at 300K and 1 atm. The simulation weres performed using MELD
with REST2 solute scaling algorithm. The lowest temperature replica was extracted and populations of
different ligands bind to receptor protein were counted. Then the relative population was derived
based on the relative population.
No
No