SECTION 2

TASS Simulation

Now that we have equilibrated starting structures corresponding to every umbrella window, umb.rst, the next step is to run 10 ns long TASS simulation for all umbrella windows i.e. apply umbrella bias along Φ1 and MTD bias along Φ2 and sample all the four coordinates (Φ1, Ψ1, Φ2, Ψ2) using high temperature.

The following input files are required for running TASS simulation for each umbrella window:

  1. ala_prmtop
  2. umb.rst*
  3. mds_tass.in
  4. plumed_tass.dat

mds_tass.in

Alanine Tri Peptide
 &cntrl
  irest=0, ntx=1,
  imin = 0, ntb = 0,
  igb = 0, ntpr = 1000, ntwx = 1000,
  ntt = 3, gamma_ln = 100.0,
  tempi = 300.0, temp0 = 300.0,
  nstlim = 10000000, dt = 0.001,
  cut=999.0, rgbmax=999.0,
plumed=1,
plumedfile='plumed_tass.dat'
&end

plumed_tass.dat

#set up four variables for Phi1, Psi1, Phi2, and Psi2 dihedral angles 
phi1: TORSION ATOMS=5,7,9,15
psi1: TORSION ATOMS=7,9,15,17
phi2: TORSION ATOMS=15,17,19,25
psi2: TORSION ATOMS=17,19,25,27
################################################################
# Impose an umbrella potential on CV 1
ex: EXTENDED_LAGRANGIAN ARG=phi1,psi1,phi2,psi2 KAPPA=5260,5260,5260,5260 TAU=0.062,0.062,0.062,0.062 FRICTION=100,100,100,100 TEMP=900
restraint-ex.phi1_fict: RESTRAINT ARG=ex.phi1_fict KAPPA=500 AT=XXXX
################################################################
# with height equal to 2.4 kJoule/mol,
# Well-tempered metadynamics is activated,
metad: METAD ARG=ex.phi2_fict PACE=500 HEIGHT=2.4 SIGMA=0.05 FILE=HILLS BIASFACTOR=4.0 TEMP=900.0
################################################################

# monitor the auxiliary variables
PRINT STRIDE=10 ARG=ex.phi1_fict,ex.psi1_fict,ex.phi2_fict,ex.psi2_fict,phi1,psi1,phi2,psi2 FILE=COLVAR
PRINT STRIDE=1000 ARG=ex.phi1_vfict,ex.psi1_vfict,ex.phi2_vfict,ex.psi2_vfict FILE=TEMP

After replacing XXXX by centre of umbrella window we want to sample, we can run each simulation through sander.

mpirun -np 2 $/AMBERHOME/bin/sander.MPI -O -i mds_tass.in -o umb_tass.out -p ala_prmtop -c umb.rst -r umb_tass.rst -x umb_tass.mdcrd

The output files of these simulations are:

  1. umb_tass.out : Output file
  2. umb_tass.rst : Output restart file with coordinates
  3. umb_tass.mdcrd : Output trajectory file
  4. COLVAR : Collective Variables file
  5. HILLS : List of added bias is stored in this file

We can make a probability distribution from the COLVAR file to insure that there is sufficient overlap between the umbrella windows.

Go through the amber tutorial and plumed tutorial for basic understanding of keywords used in mds.in and plumed.dat files. * restart file corresponds to -1.4 umbrella window