Contact Map – a package for analyzing and exploring contacts, from a trajectory generated by MD

 

Contacts can be an important tool for defining (meta)stable states in processes involving biomolecules. For example, an analysis of contacts can be particularly useful when defining bound states during a binding processes between proteins, DNA, and small molecules (such as potential drugs).

The contacts analyzed by the contact_map package can be either intermolecular or intramolecular, and can be analyzed on a residue-residue basis or an atom-atom basis.

This package makes it very easy to answer questions like:

  • What contacts are present in a trajectory?
  • Which contacts are most common in a trajectory?
  • What is the difference between the frequency of contacts in one trajectory and another? (Or with a specific frame, such as a PDB entry.)
  • For a particular residue-residue contact pair of interest, which atoms are most frequently in contact?

It also facilitates visualization of the contact matrix, with colors representing the fraction of trajectory time that the contact was present. Full documentation available at http://contact-map.readthedocs.io/.

Information about software installation, testing and a link to the source code, can be found in our E-CAM software Library here.

Practical application and exploitation of the code

The practical application of this software module is the pilot project in collaboration with BiKi Technologies on “Binding Kinetics“, sustained by an E-CAM postdoctoral researcher at University of Amsterdam.  The project aims at investigating the binding/unbinding of a selective reversible inhibitor for protein GSK3β.

Contacts between a ligand and a protein are an excellent way to characterize “hotspots” – states where the ligand stays for a significant amount of time, but not nearly as long as in the final binding pocket. These hotspots are metastable states in path sampling, and should be treated with a multiple state approach. Therefore, attempting to identify those states would be a necessarily preliminary step to prepare the path sampling simulation.

Other more general applications to this module include protein-protein aggregation or DNA-protein binding, as well as large scale conformational changes in biomolecules, such as protein folding.

 

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