Improvement of SARS-CoV-2 macromolecule conformation by algorithmic structural prediction

ABSTRACT

A fast way to reconstruct the three-dimensional molecular conformation of SARS-CoV-2 virus proteins is addressed in this article, involving the most worrying variant discovered in patients from Brazil, the lineage B.1.1.28/P.1. The proposed methodology is based on the sequencing of virus proteins and that, through the incorporation of mutations in silico, which are then computationally reconstructed using an enumerative feasibility algorithm validated by the Ramachandran diagram and structural alignment, in addition to the subsequent study of structural stability through classical molecular dynamics. From the resulting structure to the ACE2-RBD complex, the valid solution presented 97.06% of the residues in the most favorable region while the reference crystallographic structure presented 95.0%, a difference therefore very small and revealing the great consistency of the developed algorithm. Another important result was the low RMSD alignment between the best solution by the BP algorithm and the reference structure, where we obtained 0.483Å. Finally, the molecular dynamics indicated greater structural stability in the ACE2-RBD interaction with the P.1 strain, which could be a plausible explanation for convergent evolution that provides an increase in the interaction affinity with the ACE2 receptor. ©2021 IEEE