Capturing the geometry, function, and evolution of enzymes with 3D templates

TL;DR

This paper discusses methods for generating and querying 3D structural templates to identify functional sites in enzymes, aiding functional annotation and understanding enzyme evolution and catalysis.

Contribution

It introduces new algorithms for creating template libraries, querying structures, and representing flexible sites using multiple templates, enhancing enzyme function analysis.

Findings

Template libraries enable detection of conserved functional motifs.

Using multiple templates improves modeling of enzyme flexibility.

Template-based annotation will be crucial for analyzing new protein structures.

Abstract

Structural templates are 3D signatures representing protein functional sites, such as ligand binding cavities, metal coordination motifs or catalytic sites. Here we explore methods to generate template libraries and algorithms to query structures for conserved 3D motifs. Applications of templates are discussed, as well as some exemplar cases for examining evolutionary links in enzymes. We also introduce the concept of using more than one template per structure to represent flexible sites, as an approach to better understand catalysis through snapshots captured in enzyme structures. Functional annotation from structure is an important topic that has recently resurfaced due to the new more accurate methods of protein structure prediction. Therefore, we anticipate that template-based functional site detection will be a powerful tool in the task of characterising a vast number of new protein models.