Orthogonal Space Sampling Based Free Energy Perturbation
CHARMM-DOMDEC-GPU (Customized)
CGENFF/CHARMM36 force field
CHARMM CGENFF for Ligands.
Single Simulation for Each FEP Calculation
Assumed pH 7.4
Typical overall simulation length per FEP calculation (for a protein-ligand complex): 16 ns; Typical overall simulation length per FEP calculation (for a solvated ligand): 30 ns
Molecular dynamics simulation with time constant of 1 fs
(etc.)
The ligands were represented by the CHARMM CGENFF force field and the modified TIP3 water model was used.
Orthogonal space sampling (an updated version of orthogonal space tempering) based molecular dynamics calculations were performed for a target system in a periodic cube with at 300 K and 1 atm in the isothermal-isobaric ensemble using CHARMM-DOMDEC-GPU.
Orthogonal Space FEP on-the-fly Sampling
CHARMM-DOMDEC-GPU
Assumed pH 7.4
TYR365 conformation is pre-determined
HIS protonation states are pre-determined.
CHARMM generic structure preparation protocol was employed.
common reference molecule 17 is pre-equilibrated.
the structures of the other ligands dynamically evolve during Orthogonal Space Sampling FEP simulations.
No specific pre-pose prediction; structures are dynamically evolved from FEP simulations.
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