Tutorial For Temperature Accelerated Sliced Sampling

Primary Reference:

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).

Algorithm

 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  

Alanine-tiipeptide

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.

Reweighting

Compile metadynamics unbiasing code.

$ gfortran mtd_analysis_plumed_4CV.f

Prepare the input files (COLVAR, HILLS, run.sh).

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

Prepare WHAM input files (WHAMINPUT, input).

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:

<Convergence criteria>

<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)

or

$ ./wham_PLUED_4D.x

Input file: PROB_i, WHAMINPUT, input

Output file: free_energy, which contains the free energies.

                                                     ϕ1

(Projection of the reconstructed 5-dimensional free energy surface on (ϕ1, ϕ2)

plane as obtained from TASS simulation using 4 CVs)