Structural Deformability Induced in Proteins of Potential Interest Associated with COVID-19 by binding of Homologues present in Ivermectin: Comparative Study Based in Elastic Networks Models

The Z-Score showed conformational fluctuations between free protein and lowenergy ligand-protein complexes. Starting from this model, it was observed that all the Avermectins-Protein complexes presented differences in the distances of their Cα atoms, as well as in their energetics at 100 ns of simulation and with respect to their corresponding free protein subjected to the same dynamic conditions. In ProSA-web, the most extreme Z-Score values were related to more dynamic and distant conformations of the free protein. This applies both for very negative values and for values very close to 0, since they tend to fall outside the Z-Score obtained from all the protein chains determined experimentally in the Protein Data Bank (PDB). In fact, the Z-Score for proteins such as the Multidrug ABC transporter (PDB: 2HYD) has been reported to be -8.29, which is in the range of native conformations. Whereas according to the ProSA-web results obtained for the homologous ABC transporter protein of multiple drugs (PDB: 1JSQ), the Z-Score of this model is −0.60, a value too high for a typical native structure [52] . In IMPα1, the complexes with the homologues presented the most distant conformational fluctuation from the free protein one with a Z-Score more negative than that obtained for the ligand-free protein, which suggests unfolding of this protein with both stereoisomers. On the contrary, although a similar trend towards unfolding against Mpro was predicted, especially with compound..