SP-A binding to the SARS-CoV-2 spike protein using hybrid quantum and classical in silico modeling and molecular pruning by Quantum Approximate Optimization Algorithm (QAOA) Based MaxCut with ZDOCK.

Abstract

The pulmonary surfactant protein A (SP-A) is a constitutively expressed immune-protective collagenous lectin (collectin) in the lung. It binds to the cell membrane of immune cells and opsonizes infectious agents such as bacteria, fungi, and viruses through glycoprotein binding. SARS-CoV-2 enters airway epithelial cells by ligating the Angiotensin Converting Enzyme 2 (ACE2) receptor on the cell surface using its Spike glycoprotein (S protein). We hypothesized that SP-A binds to the SARS-CoV-2 S protein and this binding interferes with ACE2 ligation. To study this hypothesis, we used a hybrid quantum and classical in silico modeling technique that utilized protein graph pruning. This graph pruning technique determines the best binding sites between amino acid chains by utilizing the Quantum Approximate Optimization Algorithm (QAOA)-based MaxCut (QAOA-MaxCut) program on a Near Intermediate Scale Quantum (NISQ) device. In this, the angles between every neighboring three atoms were Fourier-transformed into microwave frequencies and sent to a quantum chip that identified the chemically irrelevant atoms to eliminate based on their chemical topology. We confirmed that the remaining residues contained all the potential binding sites in the molecules by the Universal Protein Resource (UniProt) database. QAOA-MaxCut was compared with GROMACS with T-REMD using AMBER, OPLS, and CHARMM force fields to determine the differences in preparing a protein structure docking, as well as with Goemans-Williamson, the best classical algorithm for MaxCut. The relative binding affinity of potential interactions between the pruned protein chain residues of SP-A and SARS-CoV-2 S proteins was assessed by the ZDOCK program. Our data indicate that SP-A could ligate the S protein with a similar affinity to the ACE2-Spike binding. Interestingly, however, the results suggest that the most tightly-bound SP-A binding site is localized to the S2 chain, in the fusion region of the SARS-CoV-2 S protein, that is responsible for cell entry Based on these findings we speculate that SP-A may not directly compete with ACE2 for the binding site on the S protein, but interferes with viral entry to the cell by hindering necessary conformational changes or the fusion process.