Drug binding dynamics of the dimeric SARS-CoV-2 main protease, determined by molecular dynamics simulation.

We performed molecular dynamics simulation of the dimeric SARS-CoV-2 (severe acute respiratory syndrome corona virus 2) main protease (Mpro) to examine the binding dynamics of small molecular ligands. Seven HIV inhibitors, darunavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir, and tipranavir, were used as the potential lead drugs to investigate access to the drug binding sites in Mpro. The frequently accessed sites on Mpro were classified based on contacts between the ligands and the protein, and the differences in site distributions of the encounter complex were observed among the ligands. All seven ligands showed binding to the active site at least twice in 28 simulations of 200 ns each. We further investigated the variations in the complex structure of the active site with the ligands, using microsecond order simulations. Results revealed a wide variation in the shapes of the binding sites and binding poses of the ligands. Additionally, the C-terminal region of the other chain often interacted with the ligands and the active site. Collectively, these findings indicate the importance of dynamic sampling of protein-ligand complexes and suggest the possibilities of further drug optimisations.

Thermal transistor utilizing gas-liquid transition.

We propose a simple thermal transistor, a device to control heat current. In order to effectively change the current, we utilize the gas-liquid transition of the heat-conducting medium (fluid) because the gas region can act as a good thermal insulator. The three terminals of the transistor are located at both ends and the center of the system, and are put into contact with distinct heat baths. The key idea is a special arrangement of the three terminals. The temperature at one end (the gate temperature) is used as an input signal to control the heat current between the center (source, hot) and another end (drain, cold). Simulating the nanoscale systems of this transistor, control of heat current is demonstrated. The heat current is effectively cut off when the gate temperature is cold and it flows normally when it is hot. By using an extended version of this transistor, we also simulate a primitive application for an inverter.