Name

Orthogonal Space Sampling Based Free Energy Perturbation

Software

CHARMM-DOMDEC-GPU (Customized)

Parameter

GAFF/AMBER2014SB force field
AMBER GAFF 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.)

Method

The ligands were represented by the CHARMM GAFF force field and the 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.

Name

Orthogonal Space FEP on-the-fly Sampling

Software

CHARMM-DOMDEC-GPU

System Preparation Parameters

Assumed pH 7.4
TYR365 conformation is pre-determined
HIS protonation states are pre-determined.

System Preparation Method

CHARMM generic structure preparation protocol was employed.

Pose Prediction Parameters

common reference molecule 17 is pre-equilibrated.
the structures of the other ligands dynamically evolve during Orthogonal Space Sampling FEP simulations.

Pose Prediction Method

No specific pre-pose prediction; structures are dynamically evolved from FEP simulations.
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