1146-1-76aan-PosePredictionProtocol.txt

Name

HomoLigAlign

Software

HomoLigAlign

System Preparation Parameters

refer to section "Pose Prediction Method"

System Preparation Method

Ligand tautomeric/ionization states and 3D coordinates were generated with LigPred from Schrodinger suite. Homology models with Modeller. Embeded ligand conformers with RDKit. MD simulations with AmberTools and OpenMM.

Pose Prediction Parameters

For all 20 ligands ligand a 100 ps MD simulations was conducted to equilibrate each system.

Pose Prediction Method

HomoLigAlign algorithm (still unpublished) combines homology modeling, ligand alignment and MD to generate protein-ligand poses for scoring. The algorithm starts by quering PDB for homologous proteins to the target receptor co-crystalized with ligands that are similar to those that we wish to predict their binding pose (screening compounds). Upon selecting the most appropriate structures for each screening compound, it creates a homology model of the target receptor with the original ligand. It then generates multiple conformers of the screening compound embeded on the original ligand by matching coordinates of the atoms in the maximum common substructure between those 2 molecules. Then based on some energy, shape and RMSD criteria, it selects the best embeded conformer and performs 100 ps of MD simulation in explicit solvent to equilibrate the system. The final ligand pose is the last frame of the 100 ps trajectory upon a 1000 step minimization.

Answer 1

Yes

Answer 2

Yes

1479-4-ueokh-FreeEnergyProtocol_SQM-COSMO_allWAT.txt

Name

SQM-COSMO_allWAT

Software

HomoLigAlign, SQM/COSMO

Parameter

all waters in the MD trajectory were retained for the calculations of free energies of binding.

Method

The free energies of binding were calculated using the SQM/COSMO scoring function, which is a sum of ΔEint and ΔΔGsolv terms. ΔEint term was calculated using the corrected PM6-D3H4X method on geometries with relaxed hydrogens and no close contacts. The ΔΔGsolv term is the desolvation free energy change upon binding, evaluated at the COSMO level from the PM6/COSMO calculation using MOPAC with default parameters.

Answer 1

Yes

Answer 2

No