posted on 2023-01-10, 21:07authored byBenjamin
S. Cowan, David L. Beveridge, Kelly M. Thayer
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.