all-ligands-explicit.yaml

# Set the general options of our simulation
options:
  minimize: yes
  verbose: yes
  default_number_of_iterations: 500
  temperature: 300*kelvin
  pressure: 1*atmosphere
  output_dir: all-ligands-explicit-output

# Configure the specific molecules we will use for our systems
molecules:
  # Define our receptor, T4-Lysozyme, we can call it whatever we want so we just use its name here as the directive
  t4-lysozyme:
    filepath: input/receptor.pdbfixer.pdb
  # Define our ligands
  binders:
    # This is actually a "CSV" file where the delimiter is a comma or a
    # semicolon, and each row contains the SMILES representation of a molecule.
    filepath: input/L99A-binders.csv
    antechamber:
      charge_method: bcc
    # Choose to simulate all molecules (1 at a time).
    # This is the default behavior but we specify it for this example
    select: all

# Define the solvent for our system
solvents:
  pme:
    nonbonded_method: PME
    nonbonded_cutoff: 9*angstroms
    clearance: 16*angstroms
    positive_ion: Na+
    negative_ion: Cl-

systems:
  t4-ligand:
    receptor: t4-lysozyme
    ligand: binders
    solvent: pme
    leap:
      parameters: [leaprc.protein.ff14SB, leaprc.gaff2, leaprc.water.tip4pew]
    # When ligands are generated from SMILES they have a random position.
    # Setting "pack: yes" pulls the ligand close to the receptor ensuring
    # that your solvation box won't be too big.
    pack: yes

protocols:
  absolute-binding:
    complex:
      alchemical_path:
        lambda_electrostatics: [1.00, 1.00, 1.00, 1.00, 1.00, 0.90, 0.80, 0.70, 0.60, 0.50, 0.40, 0.30, 0.20, 0.10, 0.00, 0.00, 0.00, 0.00, 0.00, 0.00, 0.00, 0.00, 0.00, 0.00, 0.00]
        lambda_sterics:        [1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 0.90, 0.80, 0.70, 0.60, 0.50, 0.40, 0.30, 0.20, 0.10, 0.00]
        # Set lambda restraints reverse of coupling parameter.
        lambda_restraints:     [0.00, 0.25, 0.50, 0.75, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00]
    solvent:
      alchemical_path:
        lambda_electrostatics: [1.00, 0.90, 0.80, 0.70, 0.60, 0.50, 0.40, 0.30, 0.20, 0.10, 0.00, 0.00, 0.00, 0.00, 0.00, 0.00, 0.00, 0.00, 0.00, 0.00, 0.00]
        lambda_sterics:        [1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 0.90, 0.80, 0.70, 0.60, 0.50, 0.40, 0.30, 0.20, 0.10, 0.00]

# Here we combine the system and the protocol to make an experiment
experiments:
  system: t4-ligand
  protocol: absolute-binding
  restraint:
    type: Harmonic # Keep the ligand near the protein