GROMACS Wizard - Umbrella Sampling#

This section is part of the GROMACS Wizard tutorial.

Use this tutorial when you want to turn a reaction-coordinate pathway into umbrella-sampling windows that can later be analyzed as a PMF.

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

Before you start#

Decide how you will obtain the starting conformations for the windows.
If you already have a pulling trajectory, follow Option 1.
If you already have conformations or a path in SAMSON, follow Option 2.

To perform Umbrella Sampling, first obtain a set of initial conformations. You can do that in one of the following ways:

From GROMACS trajectory obtained from some simulation, e.g., by performing COM pulling simulation.
From a set of conformations or a path (trajectory) created outside SAMSON or in SAMSON.

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#

Use this route if you already have a GROMACS trajectory and want to pick frames from it as the initial conformations for umbrella windows. For this tutorial, we use the results 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.

Input for Umbrella Sampling

Then specify the reaction coordinate by choosing two index groups.

Choose the reaction coordinate

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.

Choose the conformations based on the total number of conformations

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

Choose the conformations based on the COM spacing

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 conformations, click Generate project. This creates a batch project folder with a timestamp and _umbrella suffix. Each subfolder corresponds to one umbrella window, and frames.ndx records which original frames were chosen.

A folder with output

Option 2: From Conformations or Path#

Use this route when the starting states already exist in SAMSON as conformations or a path. Follow the Batch computations tutorial until the NVT equilibration step. For NPT equilibration and production MD, you will need to add the umbrella-specific COM pulling parameters described below.

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 ( Auto-fill button ) it will be set automatically based on the previous run).

Input source: batch project

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

COM pulling parameters

Once you have specified the 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 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.

Open local jobs

PMF Analysis#

Once the umbrella-sampling simulations are complete, continue with Potential of Mean Force (PMF) analysis to compute the PMF using WHAM.