Tutorial For Temperature Accelerated Sliced Sampling
See the paper: click here
Shalini Awasthi and Nisanth N. Nair “Exploring high dimensional free energy landscapes: Temperature accelerated sliced sampling”
J. Chem. Phys. 146, 094108 (2017).
Here, we briefly explain the algorithm for temperature accelerated sliced sampling (TASS) approach.
1. For the chosen range of values of s1 CV, place restraining umbrella potentials. For every umbrella, sample s2 coordinate using MTD and for rest of the CVs
no biasing potential is applied. For all the defined CVs high temperature is used.
From these simulations, obtain the time series of s1(t), s2(t), s3(t),…, sn(t) for some regular intervals of MTD time .
2. Compute for .
3. Compute for .
4. Construct the MTD–unbiased distributions.
5. Using WHAM, reweight the umbrella potential as well as combine the distribution functions to get .
6. Construct the free energy surface
To study alanine-tripeptide, we use molecular dynamics using a Langevin thermostat at 300 K, with a time step 1.0 fs, using AMBER force–field. We employed the PLUMED–AMBER interface for carrying out TASS simulations (input files: plumed_input_file, amber_input_file, topology_file, coordinate_file).
In TASS simulations, ϕ1 coordinate is sampled using US, ϕ2 coordinate is sampled using MTD bias while no bias is applied along ψ1 and ψ2.
900 K temperature was used to sample all the coordinates.
Here, Gaussian potentials are updated at every 500 fs, and kcal mol, radians and ΔT=900 K are taken. Umbrella potentials are placed from to at an interval of 0.2 radians with kcal mol rad.
Details of the input files required for simulation can be found elsewhere.
Compile metadynamics unbiasing code.
$ gfortran mtd_analysis_plumed_4CV.f
If one is using PLUMED for running simulations output files can be directly used.
(Remove commented lines from COLVAR and HILLS file.)
COLVAR file should have following information
<Time> <CV1(ϕ1)> <CV2 (ϕ2)> <CV3 (ψ1)> <CV4 (ψ2)>
HILLS file should have the following information:
<Time> <Hill position> <Hill width> <Hill height>
run.sh has following information:
-T0: (value in K) temperature of physical system. (Default: 300 K)
-T: (value in K) temperature of auxiliary variable. (Default: 300 K)
-dT (value in K) ΔT parameter used in WT-MTD. (Default:1500 K)
-tmin: step number in COLVAR file, from which reweighting
Should start. (Default:1)
-tmax : step number in COLVAR file, at which reweighting should stop
(Default: total number of steps in COLVAR file)
-grid: <gridmin1> <gridmax1> <gridsize1> of CV1,
<gridmin2> <gridmax2> <gridsize2> of CV2,…….
-pfrqMD: Number of steps after which COLVAR file is updates.
-dtMTD: Number of steps used to update bias in WTMTD
Run command run.sh for processing files from different umbrella windows.
$ sh run.sh
Output file: Probability file (Pu.dat). Rename it as PROB_i, where “i” is the umbrella index.
These PROB files contain probability of (CV1,CV2,CV3,CV4).
Collect all the PROB_i files in a folder PROB.
These PROB_i are the input for WHAM analysis.
Compile the WHAM code
$ mpif90 wham_PLUMED_4D.F90 -o wham_PLUMED_4D.x
input file contain following information:
<No. of CVs> <No. of umbrella windows> <Temperature of auxiliary variable>
<gridmin1> <gridmax1> <gridsize1> of CV1,
<gridmin2> <gridmax2> <gridsize2> of CV2,
Temperature of physical system should be provided in Kelvin. Here, grid information should be same as used during MTD unbiasing.
WHAMINPUT file contains following information:
<Probability file name of umbrella window 1>
<Position of umbrella window> <Force constant> <No of steps used for MTD unbiasing> of umbrella window 1
<Probability file name of umbrella window 2>
<Position of umbrella window> <Force constant> <No of steps used for MTD unbiasing> of umbrella window 2
<Probability file name of umbrella window h>
<Position of umbrella window> <Force constant> <No of steps used for MTD unbiasing> of umbrella window h
Run the executable (wham_PLUMED_4D.x).
$ mpirun –np 8 wham_PLUMED_4D.x (Running on 8 processors)
Input file: PROB_i, WHAMINPUT, input
Output file: free_energy, which contains the free energies.
(Projection of the reconstructed 5-dimensional free energy surface on (ϕ1, ϕ2)
plane as obtained from TASS simulation using 4 CVs)