LitCovid-sentences  

PMC:7605337 / 45013-49729 JSONTXT 7 Projects

Annnotations TAB TSV DIC JSON TextAE

Id Subject Object Predicate Lexical cue
T307 0-272 Sentence denotes The details of hydrogen bond and salt-bridge pattern in nCOV-2019 and SARS-COV to ACE2 (Table 1) are key to the virus attachment to the host. nCOV-2019 residues participate in 10 H-bonds/1 salt bridge with ACE2, whereas SARS-COV only has 5 H-bonds/1 salt bridge with ACE2.
T308 273-390 Sentence denotes This significantly contributes to ∼30 kcal/mol difference in the total binding free energy of nCOV-2019 and SARS-COV.
T309 391-767 Sentence denotes The binding energies calculated here for nCOV-2019 and SARS-COV (−50.22 ± 1.93 and −18.79 ± 1.53 kcal/mol, respectively) are in good agreement with the binding energies calculated using the generalized Born method by Spinello et al.30 Moreover, the patterns of H-bonds between nCOV-2019 and ACE2 were also already characterized by other groups26,30 which agrees with our work.
T310 768-855 Sentence denotes An important H-bond between nCOV-2019 and ACE2 is between G502 on RBD and K353 of ACE2.
T311 856-935 Sentence denotes G502 is in the L4 region, which is populated by 5 H-bonds between RBD and ACE2.
T312 936-1226 Sentence denotes The contribution of this residue to the total binding energy is −2.03 ± 0.04 kcal/mol and the Ala-substitution at G502 has the highest effect on the binding energy among all the residues by lowering the total binding affinity to 24.31 ± 2.98 kcal/mol, which is the lowest among all mutants.
T313 1227-1316 Sentence denotes This mutation breaks the other H-bonds in L4 such as H-bonds from residues Q498 and T500.
T314 1317-1440 Sentence denotes This residue is preserved and corresponds to residue G488 in SARS-COV, which also makes a H-bond with residue K353 on ACE2.
T315 1441-1552 Sentence denotes Residue Q493 in nCOV-2019 participates in binding ACE2 by making two H-bonds with residues E35 and K31 on ACE2.
T316 1553-1654 Sentence denotes Q493 corresponds to residue N479 in SARS-COV, which only makes one H-bond with residue Lys31 on ACE2.
T317 1655-1741 Sentence denotes This caused Q493 to have more contribution to total binding than its counterpart N479.
T318 1742-1956 Sentence denotes However, alanine substitution at Q493 did not affect the total binding energy and this mutant had a total binding energy similar to the wild-type complex as it maintains the number H-bonds in the wild-type complex.
T319 1957-2074 Sentence denotes Residues Q498 and T500 in nCOV-2019 are crucial for binding by making H-bonds with ACE2 residues D38, D355, and K353.
T320 2075-2188 Sentence denotes Residue Q498 corresponds to residue Y484 in SARS-COV which does not make any H-bond in the SARS-COV/ACE2 complex.
T321 2189-2322 Sentence denotes Q498 contributes to binding by −6.72 ± 0.18 kcal/mol which is more than the contribution of Y484 in SARS-COV (−1.83 ± 0.06 kcal/mol).
T322 2323-2402 Sentence denotes Ala-substitution at Q498 did not show large impact on the total binding energy.
T323 2403-2507 Sentence denotes Residue T500 is conserved and corresponds to residue T486 which also makes a H-bond with Asp355 on ACE2.
T324 2508-2585 Sentence denotes Mutation of T500 to Alanine lowers the binding affinity by about 10 kcal/mol.
T325 2586-2723 Sentence denotes Residue N487 in nCOV-2019 locates in L3 and plays a crucial role in stabilizing the recognition loop by making a H-bond with Y83 on ACE2.
T326 2724-2939 Sentence denotes This residue contributes to the total binding energy of nCOV-2019 by −1.52 ± 0.06 kcal/mol, whereas its corresponding residue in SARS-COV does not show any contribution to the binding energy (−0.02 ± 0.05 kcal/mol).
T327 2940-3080 Sentence denotes This demonstrates that L3 in SARS-COV has evolved to be an important recognition loop in nCOV-2019, which participates in binding with ACE2.
T328 3081-3234 Sentence denotes Residue K417 in nCOV-2019 has the most contribution to the total binding energy (−12.34 ± 0.23 kcal/mol by making a salt-bridge with residue D30 on ACE2.
T329 3235-3374 Sentence denotes This residue is crucial for the binding of RBD and ACE2 and alanine substitution lowers the total binding energy to −29.56 ± 2.95 kcal/mol.
T330 3375-3569 Sentence denotes This salt-bridge is found to be important for the stability of the crystal structure of the RBD/ACE2 complex in nCOV-2019.4 K417 is Val404 in SARS-COV which does not participate in binding ACE2.
T331 3570-3671 Sentence denotes Another important residue in nCOV-2019 is L455 which contributes to binding by −1.86 ± 0.03 kcal/mol.
T332 3672-3818 Sentence denotes This residue is important for hydrophobic interaction with ACE2 and mutating it to alanine lowers the total binding affinity by about 17 kcal/mol.
T333 3819-3969 Sentence denotes The hydrophobic residue F456 in nCOV-2019 also has a favorable contribution to the binding energy and F456A lowers the binding affinity by 5 kcal/mol.
T334 3970-4333 Sentence denotes These results are in fair agreement with experimental binding measurements with deep mutational scanning of RBD in nCOV-2019 where they used flow cytometry for different ACE2 concentrations to measure the dissociation constant KD.25 It was shown that mutations at K417, N487, T500, and G502 are detrimental for binding to ACE2, which agrees with the results here.
T335 4334-4605 Sentence denotes These experiments showed that mutations at Q493 and Q498 do not impact the binding affinity of RBD to ACE2 which demonstrates the high plasticity of the network of H-bonds at the interface where upon mutation at these residues the network can reshape to form new H-bonds.
T336 4606-4716 Sentence denotes Mutations at hydrophobic residues L455 and F456 are shown to reduce the binding affinity in these experiments.