Computational Identification of a Putative Allosteric Binding Pocket in TMPRSS2

Camostat, nafamostat, and bromhexine are inhibitors of the transmembrane serine protease TMPRSS2. The inhibition of TMPRSS2 has been shown to prevent the viral infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other viruses. However, while camostat and nafamostat inhibit TMPRSS2 by forming a covalent adduct, the mode of action of bromhexine remains unclear. TMPRSS2 is autocatalytically activated from its inactive form, zymogen, through a proteolytic cleavage that promotes the binding of Ile256 to a putative allosteric pocket (A-pocket). Computer simulations, reported here, indicate that Ile256 binding induces a conformational change in the catalytic site, thus providing the atomistic rationale to the activation process of the enzyme. Furthermore, computational docking and molecular dynamics simulations indicate that bromhexine competes with the N-terminal Ile256 for the same binding site, making it a potential allosteric inhibitor. Taken together, these findings provide the atomistic basis for the development of more selective and potent TMPRSS2 inhibitors.

Graph-Based Temporary Ground Wire Management in Distribution Network

It requires a large number of temporary ground wires for maintenance tasks in distribution network. Because the temporary ground wires can be grounded anywhere, it is difficult to check their states and control them. Currently solutions are generally expensive in city-scale. This paper presents a method that integrates the complex monitor, control and communication modules into a pocket computer key. The abundant of ground wires are controlled by a simple electric lock, which will downgrade the cost of whole system. This paper also proposed a graph-base temporary ground wire management algorithm, which utilizes the Boolean adjacent matrix to determine the ground operations. The experiment results show that algorithm is more efficiency the baseline of the Topological Analysis Algorithm and the Logic-based Analysis Algorithm.