LitCovid-sentences  

PMC:7605337 / 28550-35126 JSONTXT 7 Projects

Annnotations TAB TSV DIC JSON TextAE

Id Subject Object Predicate Lexical cue
T180 0-21 Sentence denotes Binding Free Energies
T181 22-526 Sentence denotes The binding energetics between ACE2 and the RBD of SARS-COV, nCOV-2019, and all its mutant complexes were investigated by the MMPBSA method.48 The binding energy was partitioned into its individual components including: electrostatic, van der Waals, polar solvation, and SASA to identify important factors affecting the interface of RBD and ACE2 in all complexes. nCOV-2019 has a total binding energy of −50.22 ± 1.93 kcal/mol, whereas SARS-COV has a much higher binding energy of −18.79 ± 1.53 kcal/mol.
T182 527-769 Sentence denotes Decomposition of binding energy to its components show that the most striking difference between nCOV-2019 and SARS-COV is the electrostatic contribution which is −746.69 ± 2.66 kcal/mol for nCOV-2019 and −600.14 ± 7.65 kcal/mol for SARS-COV.
T183 770-1074 Sentence denotes This high electrostatic contribution is compensated by a large polar solvation free energy which is 797.30 ± 3.12kcal/mol for nCOV-2019 and 659.61 ± 8.98 kcal/mol for SARS-COV. nCOV-2019 also possess a higher van der Waals (vdw) contribution (−89.93 ± 0.46 kcal/mol than SARS-COV (−70.07 ± 1.22 kcal/mol.
T184 1075-1194 Sentence denotes Furthermore, the SASA contribution to binding for SARS-COV was −8.30 ± 0.15 kcal/mol and −10.58 kcal/mol for nCOV-2019.
T185 1195-1326 Sentence denotes Both hydrophobic and electrostatic interactions play major roles in the higher affinity of nCOV-2019 RBD than SARS-COV RBD to ACE2.
T186 1327-1583 Sentence denotes The binding free energies for nCOV-2019 and SARS-COV were decomposed into a per-residue based binding energy to find the residues that contribute strongly to the binding and are responsible for higher binding affinity of nCOV-2019 than SARS-COV (Figure 7).
T187 1584-1703 Sentence denotes Most of the residues in the RBM of nCOV-2019 had more favorable contribution to the total binding energy than SARS-COV.
T188 1704-1854 Sentence denotes Residues Q498, Y505, N501, Q493, and K417 in nCOV-2019 RBM contributed more than 5 kcal/mol to binding affinity and are crucial for complex formation.
T189 1855-1944 Sentence denotes A few residues such as E484 and S494 contributed unfavorably to the total binding energy.
T190 1945-2065 Sentence denotes Among all the interface residues K417 had the highest contribution to the total binding energy (−12.34 ± 0.23 kcal/mol).
T191 2066-2236 Sentence denotes The corresponding residue in SARS-COV is V404 only had a −0.02 ± 0.01 kcal/mol contribution, which points to the importance of this residue for nCOV-2019 binding to ACE2.
T192 2237-2395 Sentence denotes Residue Q498 contributed −6.72 ± 0.18 kcal/mol and its corresponding residue in SARS-COV is a Y484 that contributed to total binding by −1.83 ± 0.06 kcal/mol.
T193 2396-2575 Sentence denotes Other important residues Y505 and N501 have more negative contribution to total binding energy than their counterparts in SARS-COV residues Y491 and T487, respectively (Figure 7).
T194 2576-2796 Sentence denotes Residue D480 in SARS-COV contributed positively to binding energy by 6.2 ± 0.15 kcal/mol and the corresponding residue in nCOV-2019 which is a S494 residue lowered this positive contribution to only 1.17 ± 0.06 kcal/mol.
T195 2797-3205 Sentence denotes Mutation D480A/G appeared to be a dominant mutation in SARS-COV in 2002–2003.51 This mutation was reported to escape neutralization by antibody 80R.52 To investigate the effect of this point mutation on binding of SARS-COV RBD to ACE2 we performed an additional simulation and calculated the binding affinity for this mutant in SARS-COV RBD with the same approach for other mutation in this study (Figure 8).
T196 3206-3337 Sentence denotes D480A mutation showed a binding affinity of 23.46 ± 3.07 kcal/mol which is about 5 kcal/mol higher than the wild-type SARS-COV RBD.
T197 3338-3545 Sentence denotes In SARS-COV, residue R426 had the highest contribution to the total binding energy (−6.27 ± 0.22 kcal/mol although the corresponding residue in nCOV-2019 is N439 with a contribution of −0.32 ± 0.02 kcal/mol.
T198 3546-3691 Sentence denotes These important mutations on RBM of nCOV-2019 from SARS-COV caused RBD of nCOV-2019 to bind ACE2 with much stronger (about 30 kcal/mol) affinity.
T199 3692-3781 Sentence denotes Figure 7 Binding energy decomposition per residue for the RBM of nCOV-2019 and SARS-COV.
T200 3782-3854 Sentence denotes Figure 8 Total free binding energy of SARS-COV, nCOV-2019, and mutants.
T201 3855-3904 Sentence denotes Natural mutants are shown with X at the bar base.
T202 3905-4011 Sentence denotes Binding free energy decomposition to its individual components for all mutants is represented in Table S2.
T203 4012-4198 Sentence denotes In all complexes, a large positive polar solvation free energy disfavors the binding and complex formation, which is compensated by a large negative electrostatic free energy of binding.
T204 4199-4238 Sentence denotes All variants had similar SASA energies.
T205 4239-4352 Sentence denotes The vdw free energy of binding ranged from −84.68 ± 0.68 kcal/mol for Q493A to −103.85 ± 0.66 kcal/mol for Y489A.
T206 4353-4590 Sentence denotes Mutant K417A had the lowest electrostatic contribution to binding −415.67 ± 5.07 kcal/mol and mutants N439K and E484A had the highest electrostatic binding contribution of −989.80 ± 5.6 kcal/mol and −941.20 ± 3.95 kcal/mol, respectively.
T207 4591-4753 Sentence denotes Most alanine substitutions exhibited similar or lower total binding affinities to nCOV-2019, however a few mutants had higher binding affinity than the wild type.
T208 4754-4884 Sentence denotes Mutant Y489A had a total binding energy of −61.78 ± 2.59 kcal/mol which was about 11 kcal/mol lower than wild type binding energy.
T209 4885-4982 Sentence denotes Mutants G446A, G447A, and T478I also demonstrated higher total binding affinities than nCOV-2019.
T210 4983-5068 Sentence denotes Other alanine substitutions had similar or lower total binding energy than nCOV-2019.
T211 5069-5184 Sentence denotes Mutant G502A has the lowest binding affinity among all the mutants with a binding energy of −24.31 ± 2.98 kcal/mol.
T212 5185-5330 Sentence denotes Mutant systems K417A, L455A, T500A, and N501A are the other mutants with total binding affinities significantly lower than the wild type complex.
T213 5331-5439 Sentence denotes The electrostatic component of binding contributes the most to the low binding affinities for these mutants.
T214 5440-5566 Sentence denotes The contribution of RBM residues to binding with ACE2 for nCOV-2019 was mapped to the RBD structure and is shown in Figure 9B.
T215 5567-5712 Sentence denotes Figure 9 (A) H bonds between RBD of nCOV-2019 and SARS-COV. (B) Mapping contribution of interface residues to structure in the RBD of nCOV-2019.
T216 5713-5754 Sentence denotes The RBD is purple and the ACE2 is yellow.
T217 5755-5932 Sentence denotes The RBD in contact with AC2 is rendered in a surface format with more red being a favorable contribution to binding (more negative) and blue unfavorable contribution (positive).
T218 5933-6045 Sentence denotes Most natural mutants exhibited similar binding affinities compared to wild-type nCOV-2019 with a few exceptions.
T219 6046-6217 Sentence denotes Mutation T478I which is one of the most frequent mutations based on the GISAID database has a binding affinity which is about 6 kcal/mol higher than that of the wild-type.
T220 6218-6302 Sentence denotes S494P and A475V showed a slightly lower binding affinity than the wild-type complex.
T221 6303-6376 Sentence denotes Other natural mutants showed binding affinities similar to wild-type RBD.
T222 6377-6576 Sentence denotes N439K demonstrated a high electrostatic energy which is compensated by large polar solvation energy and this mutant has a total binding energy of −48.27 ± 3.07 kcal/mol which is similar to nCOV-2019.