Lilien Lab
Department of Computer Science
Centre for Cellular and Biomolecular Research
University of Toronto

The same ligand is likely to bind different proteins in similar, instructive ways. Our aim is to help automate comparisons of such active sites by developing freely available, easy to use visualization software. We demonstrate a PyMOL-based structure visualization tool which utilizes ligand-based active site alignment.

Enzyme function is generally mediated by a set of molecular interactions centered around the protein's active site. In the context of protein structure and function analysis, active sites are frequently compared to identify the commonalities capable of specifying substrate binding. The current hypothesis suggests that different proteins capable of binding the same substrate should share similar interaction sites. One mechanism for identifying interaction sites relevant to protein-ligand binding is to perform ligand-based active site alignment. The variation in related active sites can help in determining which parts of the active site are necessary and which are nonessential.

Our aim is to simplify such active site comparisons by developing freely-available easy-to-use visualization software. In this work we demonstrate a structure visualization tool, employing ligand-based active site alignment. Our software is implemented in Python which allows it to be extended and interfaced to PyMOL, a well known visualization framework. We intend this version of our code to be a first step towards a more general tool for analyzing fragment binding.