Allosteric Signaling in PDZ Energetic Networks: Embedding Error Analysis

Allosteric signaling in proteins has been known for some half a century, yet how the signal traverses the protein remains an active area of research. Recently, the importance of electrostatics to achieve long-range signaling has become increasingly appreciated. Our laboratory has been working on developing network approaches to capture such interactions. In this study, we turn our attention to the well-studied allosteric model protein, PDZ. We study the allosteric dynamics on a per-residue basis in key constructs involving the PDZ domain, its allosteric effector, and its peptide ligand. We utilize molecular dynamics trajectories to create the networks for the constructs to explore the allosteric effect by plotting the heat kernel results onto axes defined by principal components. We introduce a new metric to quantitate the volume sampled by a residue in the latent space. We relate our findings to PDZ and the greater field of allostery.

Automated summary

Allosteric signaling in proteins has been an active area of research, and the importance of electrostatics in long-range signaling has been increasingly recognized. This study focuses on the allosteric dynamics of the PDZ protein, utilizing molecular dynamics trajectories to create networks and exploring the allosteric effect. A new metric is introduced to quantify the volume sampled by a residue in the latent space, providing insights into PDZ and the field of allostery.