TransAtlas:

TransAtlas Path Collective Variables 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 intermediate atomistic structures can be used as input for further biased simulations. This biased simulations can provide important information on the conformational transition path and the protein flexibility and energy required to acquire the final conformation. One of the most well-known software to compute biased MD simulations is Plumed. Plumed package is an open source library for free energy calculations in molecular systems which works together with some of the most popular molecular dynamics engines such as Amber, Gromacs and NAMD. In this tutorial, the necessary steps to go from an atomistic intermediate structure (origin) provided by TransAtlas database to another one (target), trying to go through states closer to a set of intermediate structures (path), using the method called Path Collective Variables Molecular Dynamics are presented.

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:

The necessary files to start with the Path Collective Variables PCV simulation can be downloaded clicking at the Generate button of the Path Collective Variables MD box (bottom of the page, Path Finding Techniques section). The TransAtlas generated tgz package contains 4 different files:

• Origin Frame: PDB file corresponding to the origin frame selected in the atomistic intermediate structures slider.
• Intermediate Frames: PDB file containing the set of intermediate structures (conformations).
• Plumed input configuration file: DAT file containing the minimum number of commands for plumed software to compute the biased PCV simulation.
• Auxiliar Perl script renumCaIndex.pl: PERL script to automatically reassign the same atom indexes in all intermediate structures. Note that this is extremely important for the simulation to correctly run, and it is usually needed because the MD setup process required for the origin structure typically modifies the atom indexes, mainly because new atoms (hydrogen atoms) are included.