3.1. Structural Analysis of MD Simulations
Molecular dynamics (MD) simulations were performed for the Nsp1 of
SARS-COV-2 and SARS-CoV-1. The RMSD plot indicates that both proteins
reached equilibrium after 100 ns and that the SARS-CoV-1 Nsp1 deviation
is less than the SARS-CoV-2 Nsp1. We also found that the Nsp1 F157S
variant has less stability than the wild type Nsp1 (Figure 1a). The Nsp1
SARS-CoV-1 exhibited a lower Rg values compared to the SARS-CoV-2 Nsp1.
The difference between Rg of these two proteins is
~ 0.12, which indicates functional movements of
SARS-CoV-2 Nsp1 due to the lesser compactness of the structure. In
general, the Rg for both sequences showed a determined pattern:
SARS-CoV-2 Nsp1 > SARS-CoV-1 Nsp1, as shown in Figure 1b.
The RMS plot was constructed from the 100 ns data in order to understand
the deviation of each Nsp1. The RMSF of the backbone for the SARS-CoV-2
Nsp1 displayed more flexible 164 to 170 residues (Lys, His, Ser, Ser,
Gly, Val, and Ter), as compared to the SARS-CoV-1 Nsp1 (Figure 1c). This
region corresponds to the C-terminal of the Nsp1 related to the protein
interaction with the ribosome through CT, meaning that its flexibility
could be related to its function.
In order to analyze H-bond interactions during the 100 ns simulation
time, intermolecular H-bond plots were constructed for the Nsp1 of
SARS-CoV-2 and SARS-CoV-1 (Figure 1d). We found that the SARS-CoV-2 Nsp1
has an approximately similar number of intermolecular H-bonds as the
SARS-CoV-1 Nsp1. In addition, the SASA analysis showed that the amino
acid residues of both structures approximately exhibit a similar
behavior of the hydrophilic and hydrophobic residues (Figure 1e). In
order to understand the total motion of Nsp1 structures in the phase
space, the first two eigenvectors were projected onto it. The results
indicate that the motion features characterized by the two eigenvectors
are different in the SARS-CoV-2 and SARS-CoV-1 Nsp1 proteins. As shown
in Figure 2a, SARS-CoV-2 Nsp1 show a wider motions than SARS-CoV-1 Nsp1,
indicating more conformational changes.
The plots in Figure 2b-c represent a comparative view of the Free Energy
Surface (FES) landscape as a function of RMSD and Rg for Nsp1. The
general trend applying to both Nsp1 proteins is that the higher the
value of the two parameters (RMSD and Rg), the lower the free energy
surface. We found that the Rg of SARS-CoV-2 Nsp1 is
higher than SARS-CoV-1 Nsp1, suggesting that SARS-CoV-2 Nsp1 has less
energy and more stability in compared with SARS-CoV-1 Nsp1.