I am trying to use yank to get the absolute binding free energy of a charged ion to a charged small molecule. Below is the yaml input file and the last lines from the yank output- I want to modify the NBFIX between the ion and the oxygen on the molecule so I added them to the xml file as Exceptions since I read that the CustomNonbondedForce are not correctly read in yank.
I have two files, one with ion and molecule restrained and the the other with just the ion. I have noticed that whenever I apply the restraint I get huge energies in one state, not necessarily the one with the restraint. Can someone help with this issue?
options:
minimize: yes
verbose: yes
output_dir: explicit
default_number_of_iterations: 500
temperature: 298*kelvin
pressure: 1*atmosphere
checkpoint_interval: 10
alchemical_pme_treatment: exact
resume_setup: no
resume_simulation: no
solvents:
water:
nonbonded_method: PME
nonbonded_cutoff: 12 * angstroms
switch_distance: 10 * angstroms
systems:
hydration-system:
phase1_path: [ion_mol_wat_wnbfix.xml, ../ion_mol_ionwater.pdb]
phase2_path: [ion_wat_wnbfix.xml, ../ion_ionwater.pdb]
solvent1: water
solvent2: water
ligand_dsl: resname ion
solvent_dsl: resname TIP3 or resname POT or resname CLA
charmm_parameter_files: [../../forcefield/toppar_c36_jul20/top_all36_prot.rtf,
../../forcefield/toppar_c36_jul20/par_all36m_prot.prm,
../../forcefield/toppar_c36_jul20/top_all36_lipid.rtf,
../../forcefield/toppar_c36_jul20/par_all36_lipid.prm,
../../forcefield/toppar_c36_jul20/top_all36_carb.rtf,
../../forcefield/toppar_c36_jul20/par_all36_carb.prm,
../../forcefield/toppar_c36_jul20/top_all36_cgenff.rtf,
../../forcefield/toppar_c36_jul20/par_all36_cgenff.prm,
../../forcefield/toppar_c36_jul20/toppar_water_ions_charmm.str,
../../forcefield/toppar_c36_jul20/stream/lipid/toppar_all36_lipid_model.str]
protocols:
hydration-protocol:
solvent1:
alchemical_path:
lambda_electrostatics: [1.0, 0.8, 0.6, 0.4, 0.2, 0.0, 0.0, 0.0, 0.0, 0.0, 0.0, 0.0, 0.0, 0.0, 0.0, 0.0]
lambda_sterics: [1.0, 1.0, 1.0, 1.0, 1.0, 1.0, 0.9, 0.8, 0.7, 0.6, 0.5, 0.4, 0.3, 0.2, 0.1, 0.0]
solvent2:
alchemical_path:
lambda_electrostatics: [1.0, 0.8, 0.6, 0.4, 0.2, 0.0, 0.0, 0.0, 0.0, 0.0, 0.0, 0.0, 0.0, 0.0, 0.0, 0.0]
lambda_sterics: [1.0, 1.0, 1.0, 1.0, 1.0, 1.0, 0.9, 0.8, 0.7, 0.6, 0.5, 0.4, 0.3, 0.2, 0.1, 0.0]
experiments:
system: hydration-system
protocol: hydration-protocol
restraint:
type: Harmonic
restrained_receptor_atoms: resid 0 or resid 1 or resid 2 or resid 3 # atoms of mol
restrained_ligand_atoms: resname ion # the ion
spring_constant: 10.0 * kilocalories_per_mole/(angstrom**2)
WARNING: Did not converge to within specified tolerance.
max_delta = 2.075165e-05, tol = 1.000000e-12, maximum_iterations = 10000, iterations completed = 9999
A squared uncertainty is negative. Largest Magnitude = 0.000000
A squared uncertainty is negative. Largest Magnitude = 0.000000
Free energy of solvation: 42700.919 +- 224.027 kT (25286.923 +- 132.666 kcal/mol)
DeltaG solvent1 : 957.503 +- 223.317 kT
DeltaG standard state correction: -1.540 kT
DeltaG solvent2 : 43656.882 +- 17.826 kT
Enthalpy of solvation : 115199.749 +- 1690.088 kT (68219.779 +- 1000.848 kcal/mol)
Hello,
I am trying to use yank to get the absolute binding free energy of a charged ion to a charged small molecule. Below is the yaml input file and the last lines from the yank output- I want to modify the NBFIX between the ion and the oxygen on the molecule so I added them to the xml file as Exceptions since I read that the CustomNonbondedForce are not correctly read in yank.
I have two files, one with ion and molecule restrained and the the other with just the ion. I have noticed that whenever I apply the restraint I get huge energies in one state, not necessarily the one with the restraint. Can someone help with this issue?
Thank you
Jessica B