Interactive Interface for Graph-Based Analyses of Dynamic H‑Bond Networks: Application to Spike Protein S

Dynamic
hydrogen-bond networks are key determinants of protein
conformational dynamics. In the case of macromolecular protein complexes,
which can have a large number of hydrogen bonds giving rise to extensive
hydrogen-bond networks, efficient algorithms are required to analyze
interactions that could be important for the dynamics and biological
function of the complex. We present here a highly efficient, standalone
interface designed for analyses of dynamical hydrogen-bond networks
of biomolecules and macromolecular complexes. To facilitate a comprehensive
description of protein dynamics, the interface includes analyses of
hydrophobic interactions. We illustrate the usefulness and workflow
of the interface by dissecting the dynamics of the ectodomain of SARS-CoV-2
protein S in its closed conformation. We find that protein S contains
numerous local clusters of dynamic hydrogen bonds and identify hydrogen
bonds that are sampled persistently. The receptor binding domain of
the spike protein hosts only a handful of persistent hydrogen-bond
clusters, suggesting structural plasticity. Our data analysis interface
is released here for open use.