SMOG: Structure-based Models for Biomolecules

A very brief introduction to structure-based modeling

While originally developed for the study of protein folding, over the last 15 years we have worked to extend the applicability of structure-based models to investigate a broad range of biomolecular dynamics, including domain rearrangements in proteins, folding and ligand binding in RNA and large-scale rearrangements in ribonucleoprotein assemblies (e.g. the ribosome). In its simplest form, a structure-based model defines a particular structure (typically obtained from X-ray, cryo-EM or NMR) as the global energetic minimum. Oftentimes, this single-basin description can provide rich information about complex processes. When this simple representation is insufficient to describe the process of interest, these models can be easily extended to include multiple basins of attraction, as well as describe non-specific effects (e.g. electrostatic or solvation effects). While coarse-grained variants of this model have had considerable success in expanding our understanding of protein folding, all-atom structure-based models are now widely used to study all types of biomolecules (complete descriptions can be found elsewhere). Additionally, with the computational simplicity of the models, they are proving to be very useful for structural modeling purposes, including atomic modeling of cryo-EM, SAXS and biochemical data.

To increase the accessibility of these modeling techniques, we provide the smog-server webtool, as well as the downloadable SMOG 2 software, which are able to generate SMOG models for use with Gromacs, NAMD, LAMMPS and OpenMM. While the webtool provides support for proteins, nucleic acids, and some ligands, SMOG 2 enables the application of structure-based models to any type of polymer-ligand system. For in-depth descriptions of the underlying models, and for examples of how to use the models, we refer you to the original publications and recent review articles.

How to prepare and simulate a SMOG model for a specific biomolecule

To run a single-basin structure-based model, follow these steps:

Step 0: Install Gromacs, NAMD, or openMM. Any one of these packages may be used as the engine of the simulations.

Step 1: Prepare the structure-based potential input files. (All-atom or Calpha). We have made these models freely available through our web interface. All you need to do is provide a pdb structure file and specify which parameters you would like to use, and we will generate the Gromacs input files (which are compatible with NAMD and openMM) for you.

Alternate Step 1: If you are familiar with the tool, try the standalone version SMOG 2 that can be run locally on your machine.

Step 2: Run the simulation. Due to some technical differences between structure-based models and many other commonly used models, there are a few additional considerations that will ensure maximum performance of your calculations. Click here for a details on how to run a SMOG model in Gromacs. It is highly recommended that you read this information, even if you are a simulation expert.

Step 3: Analyze the results. Once your simulations have finished, there are many forms of post-analysis that may be of interest. While there are analysis tools available with the Gromacs distribution, and VMD has a powerful Tcl scripting interface, we have also made some scripts and programs available here. If you would like to contribute analysis scripts, please send us a copy and we will make them available.

Please direct questions and comments to
Page created and maintained by Jeff Noel and Paul Whitford