Difference contact maps: From what to why in the analysis of the conformational flexibility of proteins.

Mallika Iyer,Adam Godzik,Zhanwen Li,Mayya Sedova,Lukasz Jaroszewski,Freddie Salsbury

doi:10.1371/journal.pone.0226702

Abstract

Protein structures, usually visualized in various highly idealized forms focusing on the three-dimensional arrangements of secondary structure elements, can also be described as lists of interacting residues or atoms and visualized as two-dimensional distance or contact maps. We show that contact maps provide an ideal tool to describe and analyze differences between structures of proteins in different conformations. Expanding functionality of the PDBFlex server and database developed previously in our group, we describe how analysis of difference contact maps (DCMs) can be used to identify critical interactions stabilizing alternative protein conformations, recognize residues and positions controlling protein functions and build hypotheses as to molecular mechanisms of disease mutations.

Highlights

Protein structures have complex three-dimensional shapes and are most often visualized as cartoons depicting their overall arrangement of secondary structure elements and neglecting interaction details
To identify the possible differentially stabilizing residues (DSRs) and evaluate this approach on a large set of proteins, we compared residue contact maps for conformations representing the most divergent structure models of all proteins with “redundant” structures deposited in the Protein Data Bank [8]
It is interesting to note that one of the applications of a difference contact map to the analysis of protein structural/functional conformations [14] analyzed in depth the same example as above, and despite different approach and contact definition, arrived at similar results. In this manuscript we have explored a contact map based description of protein structures with a goal of identifying residues that preferentially stabilize alternative conformations, potentially controlling the balance between different functional isoforms

Summary

Introduction

Protein structures have complex three-dimensional shapes and are most often visualized as cartoons depicting their overall arrangement of secondary structure elements and neglecting interaction details. Other visualization styles: topology diagrams [3], distance [4] or contact [5] maps are used as each of them highlights aspects of structure that are difficult to see in the other representations, but their popularity doesn’t compare to that of ribbon diagrams, which became de facto standards in presenting protein structures in manuscripts and books. Protein structures are far from static and, as any physical system in constant temperature, can assume any of the conformations from the canonical ensemble describing the system [6].

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Conclusion