Aspartate carbamoyltransferase (ATCase) is a large dodecameric enzyme with six active sites that exhibits allostery: its catalytic rate is modulated by the binding of various substrates at distal points from the active sites. A recently developed method, bond-to-bond propensity analysis, has proven capable of predicting allosteric sites in a wide range of proteins using an energy-weighted atomistic graph obtained from the protein structure and given knowledge only of the location of the active site. Bond-to-bond propensity establishes if energy fluctuations at given bonds have significant effects on any other bond in the protein, by considering their propagation through the protein graph. In this work, we use bond-to-bond propensity analysis to study different aspects of ATCase activity using three different protein structures and sources of fluctuations. First, we predict key residues and bonds involved in the transition between inactive (T) and active (R) states of ATCase by analysing allosteric substrate binding as a source of energy perturbations in the protein graph. Our computational results also indicate that the effect of multiple allosteric binding is non linear: a switching effect is observed after a particular number and arrangement of substrates is bound suggesting a form of long range communication between the distantly arranged allosteric sites. Second, cooperativity is explored by considering a bisubstrate analogue as the source of energy fluctuations at the active site, also leading to the identification of highly significant residues to the T ↔ R transition that enhance cooperativity across active sites. Finally, the inactive (T) structure is shown to exhibit a strong, non linear communication between the allosteric sites and the interface between catalytic subunits, rather than the active site. Bond-to-bond propensity thus offers an alternative route to explain allosteric and cooperative effects in terms of detailed atomistic changes to individual bonds within the protein, rather than through phenomenological, global thermodynamic arguments.

We present PyGenStability, a general-use Python software package that provides a suite of analysis and visualisation tools for unsupervised multiscale community detection in graphs. PyGenStability finds optimized partitions of a graph at different levels of resolution by maximizing the generalized Markov Stability quality function with the Louvain or Leiden algorithms. The package includes automatic detection of robust graph partitions and allows the flexibility to choose quality functions for weighted undirected, directed and signed graphs, and to include other user-defined quality functions. The code and documentation are hosted on GitHub under a GNU General Public License at https://github.com/barahona-research-group/PyGenStability.

We present an edge-based framework for the study of geometric elastic network models to model mechanical interactions in physical systems. We use a formulation in the edge space, instead of the usual node-centric approach, to characterize edge fluctuations of geometric networks defined in d-dimensional space and define the edge mechanical embeddedness, an edge mechanical susceptibility measuring the force felt on each edge given a force applied on the whole system. We further show that this formulation can be directly related to the infinitesimal rigidity of the network, which additionally permits three-and four-center forces to be included in the network description. We exemplify the approach in protein systems, at both the residue and atomistic levels of description.

Symmetric, two-sided morphology seems to argue against relativistic effects dominating compact radio emission. This kind of structure has been reported for a number of sources (Phillips and Mutel 1982; Pearson 1983) based on maps made at one frequency. Various arguments, all indirect, can be made for these sources being (1) Twin regions formed at the ends of jets which emerge from an invisible core, or (2) misidentified core-jet sources wherein the core and an unusually bright knot are wrongly taken to be a “double.” A telling test of both hypotheses is to map the sources in question over an octave or so of frequency. Proponents of view (1) would predict that the two double components will show nearly identical spectral indices and that weak central cores with flat or rising spectra might even be revealed. Champions of view (2) would predict that one end or the other will dominate at high frequencies (the core!) or that complex bridges of emission (the jet!) will be revealed between the components at low frequencies. We have followed our initial discovery of 5 symmetric compact doubles by (A) attempting to enlarge the sample of symmetric sources available to study, and (B) by investigating at 5 GHz those doubles for which the best maps exist at 1.7 GHz.

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