PMC:7605337 / 41468-43354 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7605337","sourcedb":"PMC","sourceid":"7605337","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7605337","text":"Changes in the RBD structure of nCOV-2019, SARS-COV, and mutants from their crystal structure were analyzed by RMSD and RMSF. nCOV-2019 showed a stable structure with a RMSD =1.5 Å, whereas SARS-COV had a larger RMSD value between 3–4 Å during the simulation. Most mutations of nCOV-2019 maintained similar stability to the wild-type. However, a few nCOV-2019 mutations resulted in larger deviations (\u003e2 Å), i.e., Y489A, F456A, Y505A, N487A, K417A, Y473A, and Y449A. We further investigated the structure of the extended loop domain (Figure 1B) and discovered that nCOV-2019 is stable with an RMSD of less than 1 Å, whereas the extended loop in SARS-COV shows an RMSD of about 3 Å during simulation (Figure S2). Some mutants showed high RMSD in this region. Alanine-substitution at residue N487 increased the extended loop RMSD to 2.5 Å. Other mutations that increased the extended loop RMSD (\u003e2 Å) include Y449A, G477A, and E484A. The dynamic behavior of RBD was further investigated by analyzing the RMSF of all systems. As shown in Figure 4, nCOV-2019 shows less fluctuation in L3 than SARS-COV. This is due to the presence of a four-residue motif (GQTQ) in nCOV-2019 L3, which forces the loop to adopt a compact structure by making two H-bonds (G485-C488 and Q474-G476) and thereby reducing the fluctuations in the loop. Residues F486 and N487 play major roles in stabilizing the recognition loop by making π-stacking and H-bond interactions with residue Y83 on ACE2. Alanine substitution at N487 introduced a large RMSF to L1. Mutation L472 to F486 in SARS-COV was shown to favor binding by −1.2 ± 0.2 kcal/mol using FEP.26 In addition, this mutation was shown to be among the five mutations that produce a super affinity ACE2 binder based on SARS-COV RBD.6 Alanine mutations at residues Y449, G447, and E484 increased the motion in L3 characterized by a large RMSF in this 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