Spike Protein Undeformable Motif shared by SARS-CoV-2 and SARS-CoV:
Flexible Conformations Predicted by using Deep Neural Network–based
Programs of Supersecondary Structure Codes
Abstract
A deep neural network-based program for sequence-based prediction of
supersecondary structure codes (SSSCs), called SSSCPrediction (SSSCPred)
was constructed. Furthermore, to predict the flexibility and
conformational change of proteins, a comparison program of three
deep-neural-network-based prediction systems (SSSCPred200, SSSCPred100,
and SSSCPred) was developed. I compared the predicted and observed
flexible conformations of SARS-CoV-2 and SARS-CoV spike proteins by
using SSSCs and the comparison program. The SARS-CoV SSSC sequences of
the receptor-binding motif predicted by the three
deep-neural-network-based systems well reproduced those of the Protein
Data Bank (PDB) data, including the structured loops. In contrast, the
receptor-binding motif SSSCs of SARS-CoV-2 differs greatly from those of
SARS-CoV, with that of SARS-CoV-2 being more flexible. Only one common
identical motif (SSSC: SSSHSSHHHH) among all of the compared SSSC
sequences, including predicted and observed ones, was found at the S2
subunit. This motif has an extremely rare and relatively undeformable
conformation. The comparison program may be helpful to explore
undeformable drug discovery targets of many unsolved protein structures.