forcefield_kwargs=forcefield_kwargs)
# Use Modeller to combine the protein and ligand into a complex
print('Reading protein')
protein_pdb = PDBFile(pdb_in)
print('Preparing complex')
modeller = Modeller(protein_pdb.topology, protein_pdb.positions)
print('System has %d atoms' % modeller.topology.getNumAtoms())
# This next bit is black magic.
# Modeller needs topology and positions. Lots of trial and error found that this is what works to get these from
# an openforcefield Molecule object that was created from a RDKit molecule.
# The topology part is described in the openforcefield API but the positions part grabs the first (and only)
# conformer and passes it to Modeller. It works. Don't ask why!
modeller.add(ligand_mol.to_topology().to_openmm(), ligand_mol.conformers[0])
print('System has %d atoms' % modeller.topology.getNumAtoms())
# Solvate
print('Adding solvent...')
# we use the 'padding' option to define the periodic box. The PDB file does not contain any
# unit cell information so we just create a box that has a 10A padding around the complex.
modeller.addSolvent(system_generator.forcefield,
model='tip3p',
padding=10.0 * unit.angstroms)
print('System has %d atoms' % modeller.topology.getNumAtoms())
with open(output_complex, 'w') as outfile:
PDBFile.writeFile(modeller.topology, modeller.positions, outfile)
def calculate_protein_energetics():
"""
* Create an OpenMM system using the first fragment.
* Add each fragment into the system.
* Calculate the energy of the system and print.
"""
os.chdir('group2')
# Necessary due to size of calculation
sys.setrecursionlimit(15000)
frag1 = PDBFile('frag1/no_QUP_frag1.pdb')
forcefield = ForceField(
'frag1/QUBE_pro_frag1.xml',
'frag2/QUBE_pro_frag2_plus.xml',
'frag3/QUBE_pro_frag3_plus.xml',
'frag4/QUBE_pro_frag4_plus.xml',
)
modeller = Modeller(frag1.topology, frag1.positions)
frag2 = PDBFile('frag2/no_QUP_frag2.pdb')
modeller.add(frag2.topology, frag2.positions)
frag3 = PDBFile('frag3/no_QUP_frag3.pdb')
modeller.add(frag3.topology, frag3.positions)
frag4 = PDBFile('frag4/no_QUP_frag4.pdb')
modeller.add(frag4.topology, frag4.positions)
system = forcefield.createSystem(
modeller.topology,
nonbondedMethod=NoCutoff,
)
system = apply_opls_combo(system)
integrator = LangevinIntegrator(
298.15 * unit.kelvin, # Temperature of heat bath
1.0 / unit.picoseconds, # Friction coefficient
2.0 * unit.femtoseconds, # Time step
)
platform = Platform.getPlatformByName('CPU')
simulation = Simulation(modeller.topology, system, integrator, platform)
simulation.context.setPositions(modeller.positions)
print('energy from openmm library')
print(simulation.context.getState(getEnergy=True).getPotentialEnergy())
positions = simulation.context.getState(getPositions=True).getPositions()
with open('output.pdb', 'w') as out_file:
PDBFile.writeFile(simulation.topology, positions, out_file)
structure = parmed.load_file('output.pdb')
energy_comps = parmed.openmm.energy_decomposition_system(structure, system)
total_energy = 0.0
for comp in energy_comps:
total_energy += comp[1]
print(*comp)
print(f'Total energy {total_energy: 6.6f}')
print(ligand_mol)
# can't read as PDB as "No toolkits in registry can read file"
#complex_pdb = Molecule(open('complex1.pdb', 'rb'), file_format='pdb')
# Use Modeller to combine the protein and ligand into a complex
print('Reading protein')
protein_pdb = PDBFile('protein.pdb')
# reading the ligand gives lots of warnings about "duplicate atom" but this seems incorrect
print('Reading ligand')
ligand_pdb = PDBFile('ligand1.pdb')
print('Preparing complex')
# Approach 1
modeller = Modeller(protein_pdb.topology, protein_pdb.positions)
modeller.add(ligand_pdb.topology, ligand_pdb.positions)
PDBFile.writeFile(modeller.topology, modeller.positions,
open('complex1.pdb', 'w'))
# Approach 2
# protein_pdb = parmed.load_file('protein.pdb')
# ligand_pdb = parmed.load_file('ligand1.pdb')
# complex = protein_pdb + ligand_pdb
# complex.save('complex1.pdb')
complex_pdb = PDBFile('complex1.pdb')
print('Preparing system')
forcefield_kwargs = {
'constraints': app.HBonds,
'rigidWater': True,
# Use Modeller to combine the protein and ligand into a complex
print('Reading protein')
protein_pdb = PDBFile(opt.receptor)
print('Preparing complex')
modeller = Modeller(protein_pdb.topology, protein_pdb.positions)
print('System has %d atoms' % modeller.topology.getNumAtoms())
# This next bit is black magic.
# Modeller needs topology and positions. Lots of trial and error found that this is what works to get these from
# an openforcefield Molecule object that was created from a RDKit molecule.
# The topology part is described in the openforcefield API but the positions part grabs the first (and only)
# conformer and passes it to Modeller. It works. Don't ask why!
if len(other_mols) != 0:
for other_mol in other_mols:
modeller.add(other_mol.to_topology().to_openmm(),
other_mol.conformers[0])
#modeller.add(ligand_mol.to_topology().to_openmm(), ligand_mol.conformers[0])
# Generate ligand with solvent for FEP
if opt.ligand:
modeller_org = Modeller(ligand_mol.to_topology().to_openmm(),
ligand_mol.conformers[0])
modeller_org.addSolvent(system_generator.forcefield,
model='tip3p',
ionicStrength=0.1 * unit.molar,
padding=10.0 * unit.angstroms)
system_org = system_generator.create_system(modeller_org.topology,
molecules=ligand_mol)
system_org.addForce(
openmm.MonteCarloBarostat(1 * unit.atmospheres, opt.temp * unit.kelvin,
25))