Thermal response of main protease of SARS and COVID-19 via a coarse-grained approach

Abstract

Large-scale Monte Carlo simulations are performed to investigate local and global thermodynamic properties of the main protease in SARS (MP1) and COVID-19 (MP2) coronaviruses using a bond-fluctuating coarse-grained protein model for a range of temperatures. Each of the proteins MP1 and MP2 consists of 306 residues with only 12 specific sites differentiating the two. Thermal responses of the radius of gyration of MP1 and MP2 are very similar. On raising the temperature, the radius of gyration of both MP1 and MP2 exhibits a slow decay in the sub-native regime and reaches a minimum at a characteristic temperature beyond which it increases continuously before saturating at high temperatures to random-coil conformations. The variation of the root mean square displacement of the center of mass of MP1 and MP2 with the time step is also similar to a function of temperature, except that MP2 slows down more than MP1 at low temperatures. Average contact profiles (and complementary mobility profiles) of MP1 and MP2 show their unique segmental globularity, which reduces on raising the temperature, in general, with a distinct trend around few residues. For example, a considerable high degree of contacts is found around residue K180 of MP1 than around residue N180 of MP2, in contrast to higher contacts around residue L286 of MP2 than around I286 of MP1. The changes in contacts of residues V86 and K88 in MP2 with respect to those of residues L86 and R88 in MP1 are also appreciable, but not as large. Distinctions in segmental structures triggered by unique contacts of MP1 and MP2 may be a factor in distinguishing the viral effects of SARS and COVID-19.