Sites and Zones of Maximum Reactivity of the most Stable Structure of the Receptor-binding Domain of Wild-type SARS-CoV-2 Spike Protein: A Quantum Density Functional Theory Study

Abstract

Today, it is well known that Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has four types of proteins within its structure, between them the spike protein (S). The infection mechanism is carried out by the entry of the virus into the human host cell through the S protein, which strongly interacts with the human cell receptor angiotensin-converting enzyme 2 (ACE2). In this work, we propose an atomic model of the Receptor Binding Domain (RBD) of the S spike protein of the wild-type SARS-CoV-2 virus. The molecular structure of the model was composed of 50 amino acids that were chemically bonded, starting with Leucine and ending with one amino acid Tyrosine. The novelty of our work lies in the importance of knowing the sites and zones of maximum reactivity of the RBD from the fundamental levels of quantum mechanics considering the atomic structure of matter. For this, the local and global reactivity indices of the RBD were calculated, such as frontier orbitals, Highest Occupied Molecular Orbital (HOMO) and Lowest Unoccupied Molecular Orbital (LUMO), Fukui indices, chemical potential, chemical hardness, electrophilicity index; with this, it will be possible to know what type of molecules are more likely to interact with the RBD structure, and in this way, new knowledge will be generated at the quantum, atomic and molecular level to inhibit the virulent effects of wild-type SARS-CoV-2. Finally, in order to identify the functional groups within the most stable structure and thereby verify the future reactions that can be carried out between the RBD structure and biomolecules, the Infrared (IR) absorption spectrum was calculated. For this work, we used Material Studio v6.0 which uses the density functional theory (DFT) implemented in its DMol3 computational code. The IR spectrum was obtained using the Spartan ‘94 computer code. One novelty would be that we found nine amino acids more that could make the RBD and ACE2 binding further the already known. Thus, the Mulliken charge distribution indicates that the highest concentrations of positive and negative charge are found in the zones 477S, 478T, 484E, and 501N amino acids letting ionic or Van der Waals possible interactions with other structures.