Property map collective variable as a useful tool for force field correction
Dalibor Trapl, Martin Krupička, Vladimir Višňovský, Jana Hozzová,
Jaroslav Olha, Aleš Křenek, and Vojtěch Spiwok

Molecular mechanics potentials for small molecules suffer inaccuracies.
To apply corrections we used a concept called property map to calculate
corrections. It was calculated as a sum of
[correction_i exp(-lambda D(x, x_i))] divided by the sum of
[exp(-lambda D(x, x_i))], where correction_i is the difference between
the accurate and inaccurate potential for i-th landmark structure x_i,
lambda is a chosen prefactor, D is a distance (e.g. RMSD or MSD) and
x are atomic coordinates. The concept was tested on alanine dipeptide
(all combinations of 7 force fields, one used as a model of accurate and
one as inaccurate). Next it was applied on an anticancer drug Imatinib
(General AMBER Force Field corrected to DFT).

Simulations were carried out in Gromacs 2016.4. Correction was
Implemented using Plumed 2.4. DFT energies were calculated by ORCA
4.0 at the BP86/def2-TZVP level of theory.

aladip/
Each directory contains Gromacs topology (topol.top), input structures
(npt.cpt, npt.gro) and instructions (md.mdp), property map input and
reference structure (plumed.dat, reference.pdb), gromacs_commands.sh
script to run the simulations for metadynamics simulations and output
HILLS file.
  FES_03to03_wat/
    Free energy surface of alanine dipeptide in Amber03 corrected to
    Amber03.
  FES_03to94_wat/
    Free energy surface of alanine dipeptide in Amber03 corrected to
    Amber94.
  FES_03to96_wat/
    Free energy surface of alanine dipeptide in Amber03 corrected to
    Amber96.
  FES_03to99SBILDN_wat/
    Free energy surface of alanine dipeptide in Amber03 corrected to
    Amber99SBILDN.
  FES_03to99SB_wat/
    Free energy surface of alanine dipeptide in Amber03 corrected to
    Amber99SB.
  FES_03to99_wat/
    Free energy surface of alanine dipeptide in Amber03 corrected to
    Amber99.
  FES_03toGS_wat/
    Free energy surface of alanine dipeptide in Amber03 corrected to
    AmberGS.
  FES_94to03_wat/
    Free energy surface of alanine dipeptide in Amber94 corrected to
    Amber03.
  FES_94to94_wat/
    Free energy surface of alanine dipeptide in Amber94 corrected to
    Amber94.
  FES_94to96_wat/
    Free energy surface of alanine dipeptide in Amber94 corrected to
    Amber96.
  FES_94to99SBILDN_wat/
    Free energy surface of alanine dipeptide in Amber94 corrected to
    Amber99SBILDN.
  FES_94to99SB_wat/
    Free energy surface of alanine dipeptide in Amber94 corrected to
    Amber99SB.
  FES_94to99_wat/
    Free energy surface of alanine dipeptide in Amber94 corrected to
    Amber99.
  FES_94toGS_wat/
    Free energy surface of alanine dipeptide in Amber94 corrected to
    AmberGS.
  FES_96to03_wat/
    Free energy surface of alanine dipeptide in Amber96 corrected to
    Amber03.
  FES_96to94_wat/
    Free energy surface of alanine dipeptide in Amber96 corrected to
    Amber94.
  FES_96to96_wat/
    Free energy surface of alanine dipeptide in Amber96 corrected to
    Amber96.
  FES_96to99SBILDN_wat/
    Free energy surface of alanine dipeptide in Amber96 corrected to
    Amber99SBILDN.
  FES_96to99SB_wat/
    Free energy surface of alanine dipeptide in Amber96 corrected to
    Amber99SB.
  FES_96to99_wat/
    Free energy surface of alanine dipeptide in Amber96 corrected to
    Amber99.
  FES_96toGS_wat/
    Free energy surface of alanine dipeptide in Amber96 corrected to
    AmberGS.
  FES_99SBILDNto03_wat/
    Free energy surface of alanine dipeptide in Amber99SBILDN
    corrected to Amber03.
  FES_99SBILDNto94_wat/
    Free energy surface of alanine dipeptide in Amber99SBILDN
    corrected to Amber94.
  FES_99SBILDNto96_wat/
    Free energy surface of alanine dipeptide in Amber99SBILDN
    corrected to Amber96.
  FES_99SBILDNto99SBILDN_wat/
    Free energy surface of alanine dipeptide in Amber99SBILDN
    corrected to Amber99SBILDN.
  FES_99SBILDNto99SB_wat/
    Free energy surface of alanine dipeptide in Amber99SBILDN
    corrected to Amber99SB.
  FES_99SBILDNto99_wat/
    Free energy surface of alanine dipeptide in Amber99SBILDN
    corrected to Amber99.
  FES_99SBILDNtoGS_wat/
    Free energy surface of alanine dipeptide in Amber99SBILDN
    corrected to AmberGS.
  FES_99SBto03_wat/
    Free energy surface of alanine dipeptide in Amber99SB corrected
    to Amber03.
  FES_99SBto94_wat/
    Free energy surface of alanine dipeptide in Amber99SB corrected
    to Amber94.
  FES_99SBto96_wat/
    Free energy surface of alanine dipeptide in Amber99SB corrected
    to Amber96.
  FES_99SBto99SBILDN_wat/
    Free energy surface of alanine dipeptide in Amber99SB corrected
    to Amber99SBILDN.
  FES_99SBto99SB_wat/
    Free energy surface of alanine dipeptide in Amber99SB corrected
    to Amber99SB.
  FES_99SBto99_wat/
    Free energy surface of alanine dipeptide in Amber99SB corrected
    to Amber99.
  FES_99SBtoGS_wat/
    Free energy surface of alanine dipeptide in Amber99SB corrected
    to AmberGS.
  FES_99to03_wat/
    Free energy surface of alanine dipeptide in Amber99 corrected to
    Amber03.
  FES_99to94_wat/
    Free energy surface of alanine dipeptide in Amber99 corrected to
    Amber94.
  FES_99to96_wat/
    Free energy surface of alanine dipeptide in Amber99 corrected to
    Amber96.
  FES_99to99SBILDN_wat/
    Free energy surface of alanine dipeptide in Amber99 corrected to
    Amber99SBILDN.
  FES_99to99SB_wat/
    Free energy surface of alanine dipeptide in Amber99 corrected to
    Amber99SB.
  FES_99to99_wat/
    Free energy surface of alanine dipeptide in Amber99 corrected to
    Amber99.
  FES_99toGS_wat/
    Free energy surface of alanine dipeptide in Amber99 corrected to
    AmberGS.
  FES_GSto03_wat/
    Free energy surface of alanine dipeptide in AmberGS corrected to
    Amber03.
  FES_GSto94_wat/
    Free energy surface of alanine dipeptide in AmberGS corrected to
    Amber94.
  FES_GSto96_wat/
    Free energy surface of alanine dipeptide in AmberGS corrected to
    Amber96.
  FES_GSto99SBILDN_wat/
    Free energy surface of alanine dipeptide in AmberGS corrected to
    Amber99SBILDN.
  FES_GSto99SB_wat/
    Free energy surface of alanine dipeptide in AmberGS corrected to
    Amber99SB.
  FES_GSto99_wat/
    Free energy surface of alanine dipeptide in AmberGS corrected to
    Amber99.
  FES_GStoGS_wat/
    Free energy surface of alanine dipeptide in AmberGS corrected to
    AmberGS.
  fes/
    Collected free energy surfaces (files with 65536 lines to be
    converted to 256x256 grid), regions with free energy >30 kJ/mol
    were set to 30 kJ/mol.
  dftb/
    CP2K input files for metadynamics at the DFTB/MM level (MD input
    and energy input files, input structre, AMBER MM topology etc.)
    for a two-step equilibration and metadynamics.
  rmse.R
    R script to calculate RMSE between precalculated corrected free
    energy surfaces located in fes/ and reference free energy surfaces
    located in fes/control
  diffs.txt
    Output of rmse.R script, RMSE values between corrected free energy
    surfaces and control reference surfaces

imatinib/
  without_correction/
    Gromacs topology (MOL_GMX.top), input structures (npt.cpt,
    npt.gro) and instructions (mtd.mdp) for molecular dynamics
    simulations of Imatinib in water.
  correction/
    Gromacs topology (MOL_GMX.top), input structures (npt.cpt,
    npt.gro), instructions (mtd.mdp), property map input and
    reference structure (plumed.dat, reference.pdb) for molecular
    dynamics simulations of Imatinib in water.