GROMACS Wizard – Umbrella Sampling

This section is a part of the GROMACS Wizard tutorial.

This tutorial demonstrates how to perform Umbrella Sampling using GROMACS Wizard.

To perform Umbrella Sampling you first need to obtain a set of initial conformations. You can do it in one of the following ways:

Then you need to perform NPT equilibration and production MD simulation with specific COM pulling parameters for the reaction coordinate or coordinates you want to analyze.

Once the simulation is done, you can perform PMF analysis.

 

Option 1: From GROMACS Trajectory

If you already have a GROMACS trajectory from which you would like to use frames as initial conformations for Umbrella Sampling then read this section. For the tutorial’s sake, we will use the results obtained from the COM Pulling tutorial.

Generate Umbrella Sampling Project

Switch to the Umbrella Sampling tab in the GROMACS Wizard.

Choose the input project – this will automatically identify the trajectory file from the project folder.

Then specify the reaction coordinate by choosing two index groups.

Note: You can add custom index groups that might later be useful for analysis or during the simulation (e.g., as pull coordinate groups). Please refer to Step 1: Prepare – Adding custom index groups.

You should see the reaction coordinate plot showing distance vs time with the suggested initial conformations depicted via vertical and horizontal dashed lines.

Now, specify the spacing between initial conformations. You have two options:

  • Number of conformations – the conformations will be equidistributed along the reaction coordinate.

  • Minimum COM spacing – the conformations will be chosen to satisfy the specified center of mass (COM) distance.

Note: you can also specify the start and end frames between which the initial conformations should be chosen.

Once you choose the spacing for initial conformation click “Generate project“. This will generate a batch project folder with a timestamp and “_umbrella” suffix that contains subfolders with individual projects per initial conformation and “frames.ndx” file with information on which frames from the original trajectory were chosen as the initial conformations for Umbrella Sampling.

 

Option 2: From Conformations or Path

Please refer to the Batch computations tutorial and follow it until the NVT equilibration step including. For NPT equilibration and production MD simulation you need to specify in COM pulling the reaction coordinates you want to analyze – see the next section.

 

NPT Equilibration and Simulation

Now, you can perform NPT equilibration (see Step 4: NPT Equilibration) and then production MD simulation (see Step 5: Production Molecular Dynamics Simulation) for this batch project.

Note: You need to run NPT equilibration with the added COM Pulling parameters since they modify the system’s behavior.

In these steps, choose the batch project as the input path (if you click the auto-fill button it will be set automatically based on the previous run).

Apart from other parameters, you need to set the COM pulling parameters for the reaction coordinate or coordinates you want to analyze. For each of the steps, NPT equilibration and Simulation, in the advanced parameters window set the COM pulling parameters as needed and set the rate to 0. For this tutorial, we set them as follows – we use a single reaction coordinate for the distance between the center of masses of chain A and chain B while setting the rate to 0 to omit the actual pulling itself:

  • type: umbrella
  • geometry: distance
  • group 1: chain A
  • group 2: chain B
  • start: yes
  • distance: N N Y (i.e., pulling in the z-direction)
  • init: 0 nm
  • rate: 0 nm/ps (i.e., no pulling)
  • force constant: 1000 kJ mol^-1 nm^-2

Once you specified parameters, launch the computations locally or in the Cloud (see Launching computations in the Cloud).

Note that when launching local computations for a batch project they will be added as local jobs – a separate job per a subfolder in the batch project – you can access them in the Local jobs window and see their status, change their priority (order), cancel or stop them, import them or open their folders.

 

PMF Analysis

Once you performed the Umbrella Sampling simulation, you can use GROMACS Wizard to compute the Potential of Mean Force (PMF) using the Weighted Histogram Analysis Method (WHAM). Please refer to the Potential of Mean Force (PMF) analysis tutorial.

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