TransAtlas:

TransAtlas Atomistic MD Tutorial

TransAtlas database contains more than 8 million different atomistic structures reconstructed from the intermediate frames obtained for the set of conformational transitions computed (see Atomistic Analysis section). These atomistic structures can be used to obtain further flexibility information by means of atomistic Molecular Dynamics simulations. However, and unlike the majority of the Coarse-Grained methods, atomistic Molecular Dynamics simulations require a previous setup of the structure before being ready to be used as input. This setup involves a number of steps such as the addition of solvent molecules surrounding the protein and counterions to neutralize the system, as well as energetic minimization steps to slowly equilibrate the system with the newly added molecules until reaching an energetically stable system to start the simulation with. In order to ease this setup process, TransAtlas is coupled to MDWeb server. MDWeb server is a tool to setup, run and analysis protein Molecular Dynamics simulations on web. Information about the web server, functionalities and tutorials can be found here: MDWeb help pages. In this tutorial, the necessary steps to go from an atomistic intermediate structure provided by TransAtlas database to a system ready to be used as input in a Molecular Dynamics package using MDWeb are presented. The system can be prepared to run in three of the most famous and widely-used MD packages: Gromacs, Amber and NAMD.

The first step in this tutorial is to choose the intermediate atomistic structure we are interested in. For that, we need to go to the Atomistic Analysis tab in the TransAtlas results.

To reach this Atomistic Analysis tab, we need to first choose a particular conformational transition from TransAtlas database. For that, we can use any of the search possibilities offered by the web server (see Search help sections). In order to use a quick and easy example to ilustrate this step, we can use the Quick Search box placed in the top-right part of the web server:

If we write the PDB code 1ba2 (a mutant of a d-ribose-binding protein, well-known to be an open state of a conformational transition) in the Quick Search box and type the return key, TransAtlas interface will send us to the results tab of the Search section:

Once there, we are going to choose the first result, the one corresponding to the conformational transition cluster representative 1ba2_A to 1urp_A:

From the different information found in the results box, the small grey box with icons inside is the one that links the conformational transition to the set of TransAtlas analysis. In particular, clicking on the magnifier icon will send us straight to the Atomistic Analysis:

Now, we can already choose a particular atomistic intermediate structure from the set of 5 frames (in this particular case, the number of intermediate structures varies with every conformational transition). To select a particular structure, the origin white square on the slider (that is placed on the frame number 1 by default) can be moved to the right. When the slider is moved, the corresponding structure box placed just below is automatically modified with the new frame number, the difference in RMSd from the origin and target structures, the structure to be used in the visualization with JSMol and to be downloaded, and the atomistic MD setup with MDWeb. The second step in this tutorial is the connection between TransAtlas and MDWeb. For that, and once we have confirmed that the chosen structure is the one that we are interested in (visualizing it with JSMol, or downloading it), we can click on the MDWeb icon That will open a new window, that is the bridge from TransAtlas to MDWeb:

In this bridge window, it is possible to enter an already existing MDWeb user account, or work as an anonymous user (no password needed for working as anonymous). Work with a registered MDWeb user is strongly recommended (see MDWeb users). After this bridge window, the chosen TransAtlas intermediate atomistic structure will be directly uploaded to the MDWeb server, and will be registered in the user's workspace, clearly identified as being a TransAtlas Conformational Transition Structure, with the name of the conformational transition, and the corresponding frame number:

Finally, the last step for the preparation of the structure to run an atomistic MD simulation is to follow the MDWeb Setup Tutorial explained step by step in the corresponding MDWeb help section. This tutorial will guide you through the few easy steps needed to run a complete setup with Gromacs, Amber or NAMD to the structure that has been already uploaded from TransAtlas database. After this step is done, the prepared system (with counterions, solvent molecules, and energetically equilibrated) can be downloaded and used to start the atomistic MD simulation. If you are not familiar with this process, MDWeb is also able to prepare the configuration files needed to run the MD for the three different MD packages, and provide them to the user. This information can be found in the MDWeb Run Tutorial, in the corresponding MDWeb help section.