construction and visualization of transition pathways

Download SmoothT via Github

SmoothT is a software for the construction of low-energy transition pathways from previously calculated ensembles of conformations. It was developed in the context of Monte Carlo (MC) simulations, namely protein folding and docking, but has not inherent limitation towards these applications. The connectivity is detected by RMSD from ensembles of MC conformations. The resulting pathways allow to estimate energy barriers between macro states. A refinement of the energy profiles along the path is provided by SmoothT by means of a simple approximation of local barriers between neighboring MC conformers.
Below is an example of a pathway that was constructed from an extensive all-atom molecular dynamics simulation.
(Scroll down for additional information.)

This pathway was derived from ~20k PDB snapshots of a ... ms MD simulation of ... MD simulations are generally performed with a fixed frequency of writing the current conformation into a trajectory file. Ligands will move faster while moving freely through solution, compared to them being in contact with the receptor. Therefore, we applied a two step process with two different RMSDs. First, we created a pathway using a high RMSD value for neighbor detection. This allows to connect snapshots with rather larger RMSD between them while being unbound. The second phase with lower neighbor distance starts from a point, where the ligand is in touch with the receptor.
The final low energy pathway consists of snapshots/poses with a defined energy value. These can be plotted in terms of a simple connection:

The steps leading from one to the next node in the path are unknown. Nonetheless it is possible to estimate possible energy barriers, between neighboring nodes.

To illustrate the construction of the transition, see the following image.

Download SmoothT via Github