LitCovid-sentences  

PMC:7605337 / 19981-40490 JSONTXT 8 Projects

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Id Subject Object Predicate Lexical cue
T102 0-7 Sentence denotes Results
T103 9-28 Sentence denotes Structural Dynamics
T104 29-262 Sentence denotes To compute the RMSD of systems, the rotational and translational movements were removed by first fitting the Cα atoms of the RBD to the crystal structure and then computing the RMSD with respect to the Cα atoms of RBD in each system.
T105 263-352 Sentence denotes Figure 3 shows the RMSD plot in the RBD of SARS-COV, nCOV-2019, and some of its variants.
T106 353-473 Sentence denotes Comparison of the RMSD of SARS and nCOV-2019 RBD shows that SARS-COV has a larger RMSD throughout the 500 ns simulation.
T107 474-643 Sentence denotes In nCOV-2019, the RMSD is very stable with a value of about 1.5 Å, whereas in SARS-COV, the RMSD increases up to ∼4 Å after 100 ns and then fluctuates between 3 and 4 Å.
T108 644-749 Sentence denotes The change in RMSD of SARS is partially related to the motion in the C-terminal which is a flexible loop.
T109 750-831 Sentence denotes Figure 3 Cα RMSD plots for nCOV-2019 and SARS-COV and a few nCOV-2019 mutations.
T110 832-912 Sentence denotes The RMSD plots for the nCOV-2019 mutants show similar behaviors to nCOV-2019-wt.
T111 913-1054 Sentence denotes In most of the variants, the RMSD is very stable during the 300 ns simulation which shows the great tolerance of the interface for mutations.
T112 1055-1106 Sentence denotes However, a few mutations showed some RMSD variance.
T113 1107-1194 Sentence denotes In mutation Y489A, the RMSD increases from 1.37 ± 0.21 Å to1.88 ± 0.16 Å after 2000 ns.
T114 1195-1307 Sentence denotes Mutation Y505A resulted in an increase in RMSD up to 100 ns to a value to 1.98 ± 0.20 Å and decreased afterward.
T115 1308-1395 Sentence denotes The RMSD for mutation N487A shows an increasing behavior with a value of 2.10 ± 0.23 Å.
T116 1396-1461 Sentence denotes Mutations N439K, V483A, and V483F showed a stable RMSD of ∼1.5 Å.
T117 1462-1538 Sentence denotes For mutations T478I, G476S, S494P, and A475V, the RMSD increases up to ∼2 Å.
T118 1539-1641 Sentence denotes These variations in the backbone RMSD show the involvement of these residues in the complex stability.
T119 1642-1696 Sentence denotes RMSD plots for other mutations are shown in Figure S1.
T120 1697-1898 Sentence denotes Since the extended loop (residues 449 to 510 shown in Figure 1B from α4 to α5) of the RBD makes all contacts with ACE2, the RMSD was computed by also fitting to the Cα atoms of this region (Figure S2).
T121 1899-2069 Sentence denotes The extended loop in nCOV-2019 is very stable with less deviation (RMSD = 0.86 ± 0.017 Å) from the crystal structure compared to SARS-COV having an RMSD of 2.79 ± 0.05 Å.
T122 2070-2145 Sentence denotes Few of the mutants show an increase in the loop RMSD during the simulation.
T123 2146-2293 Sentence denotes In mutants N487A and Y449A the loop RMSD jumps to a value of about 1.95 ± 0.12 Å and 1.94 ± 0.24 Å, respectively, after about 200 ns of simulation.
T124 2294-2414 Sentence denotes Mutants G447A and E484A show a loop RMSD values of 2.22 ± 0.03 Å and 1.96 ± 0.02 Å during the last 100 ns of simulation.
T125 2415-2501 Sentence denotes Other mutants showed a stable extended loop (observed in loop RMSD) during simulation.
T126 2502-2602 Sentence denotes The stability of extended loop for mutant systems confirms the high tolerance of this region of RBD.
T127 2603-2739 Sentence denotes To characterize the dynamic behavior for each amino acid in the RBD, we analyzed the root mean square fluctuation (RMSF) of all systems.
T128 2740-2883 Sentence denotes The RMSF plots for nCOV-2019, SARS-COV, and four other mutations are shown in Figure 4. nCOV-2019 shows less fluctuations compared to SARS-COV.
T129 2884-3026 Sentence denotes L3 in nCOV-2019 corresponding to residues 476 to 487 (shown in red in Figure 4) has smaller RMSF (1.5 Å) than SARS-COV L3 residues 463 to 474.
T130 3027-3109 Sentence denotes L1 in both nCOV-2019 and SARS-COV (green) has small fluctuation (less than 1.5 Å).
T131 3110-3205 Sentence denotes Moreover, the C-terminal residues of SARS-COV show high fluctuation (Figure 4 shown in orange).
T132 3206-3252 Sentence denotes Few mutants show higher fluctuation in the L1.
T133 3253-3350 Sentence denotes Mutants Y505A and S494A had a RMSF of 2.5 Å and mutation N487A had a RMSF of about 4 Å in the L1.
T134 3351-3407 Sentence denotes Mutation Y449A has a higher RMSF of about 3 Å in the L3.
T135 3408-3489 Sentence denotes Mutants G496A, E484A, and G447A show a high fluctuation of about 4.5 Å in the L3.
T136 3490-3539 Sentence denotes The RMSF of other variants is shown in Figure S3.
T137 3540-3620 Sentence denotes Figure 4 RMSF plots for nCOV-2019-wt, SARS-COV, Y505A, N487A, G496A, and E484A.
T138 3621-3727 Sentence denotes The red shaded region shows the fluctuation in L1 and the green shaded region shows the fluctuation in L3.
T139 3728-3805 Sentence denotes The orange shaded region in SARS-COV shows the fluctuation in the C-terminal.
T140 3806-3879 Sentence denotes For comparison, the RMSF of nCOV-2019-wt is shown as cyan in other plots.
T141 3881-3893 Sentence denotes PCA and aFEL
T142 3894-3994 Sentence denotes To identify the dominant motions in the nCOV-2019, SARS-COV, and all the mutants, PCA was performed.
T143 3995-4200 Sentence denotes Most of the combined motions were captured by the first ten eigenvectors generated from the last 400 ns for SARS-COV, nCOV-2019, and extended mutant systems and the last 200 ns for other nCOV-2019 mutants.
T144 4201-4315 Sentence denotes The percentage of the motions captured by the first three eigenvectors was 51% for nCOV-2019 and 68% for SARS-COV.
T145 4316-4409 Sentence denotes In all mutations, more than 50% of the motions were captured by the first three eigenvectors.
T146 4410-4570 Sentence denotes The first few PC’s describe the highest motions in a protein which are related to a functional motion such as binding or unbinding of protein from the receptor.
T147 4571-4770 Sentence denotes The first three eigenvectors were used to calculate the aFEL using the last 400 ns of simulation for nCOV-2019 and SARS-COV as shown in Figure 5, which displays the variance in conformational motion.
T148 4771-4869 Sentence denotes SARS-COV showed two distinct low free energy states shown as blue separated by a metastable state.
T149 4870-4971 Sentence denotes There is a clear separation between the two regions by a free energy barrier of about 6–7.5 kcal/mol.
T150 4972-5087 Sentence denotes These two states correspond to the loop motions in the L3 as well as the motion in C-terminal residues of SARS-COV.
T151 5088-5236 Sentence denotes The L3 motion in nCOV-2019 is stabilized by the H-bond between N487 on RBD and Y83 on ACE2 as well as a π-stacking interaction between F486 and Y83.
T152 5237-5433 Sentence denotes It is evident that the nCOV-2019 RBD is more stable than SASR-COV RBD and exists in one conformation whereas the SARS-COV interface fluctuates and the aFEL is separated into two different regions.
T153 5434-5655 Sentence denotes The first two eigenvectors were used to calculate and plot the aFEL as a function of first two principal components using the last 200 ns of the simulation for mutant systems. aFEL for other systems is shown in Figure S4.
T154 5656-5815 Sentence denotes Figure 5 Mapping of the principal components of the RBD for the aFEL from the last 400 ns of simulations for SARS-COV (top row) and nCOV-2019-wt (bottom row).
T155 5816-5874 Sentence denotes The color bar is relative to the lowest free energy state.
T156 5875-6153 Sentence denotes In each system, the first eigenvector was used to construct the porcupine plots to visualize the most dominant movements (Figure S5). nCOV-2019 showed a small motion in L3 and the core region and the extended loop region are very rigid showing small cones in the porcupine plot.
T157 6154-6259 Sentence denotes The core structure of the RBD remains dormant as the cones are blue in most of the regions (Figure S5-A).
T158 6260-6329 Sentence denotes In SARS-COV, the C-terminal region shows large motions (Figure S5-B).
T159 6330-6387 Sentence denotes Mutation N487A showed a large motion in L1 (Figure S5-C).
T160 6388-6466 Sentence denotes Mutations Y449A, G447A, and E484A demonstrate large motions in L3 (Figure S5).
T161 6467-6576 Sentence denotes Overall, these plots show the involvement of these residues in the dynamic stability of the RBD/ACE2 complex.
T162 6578-6582 Sentence denotes DCCM
T163 6583-6829 Sentence denotes The correlated motions of RBD atoms were also analyzed with the DCCM based on the Cα atoms of RBD from the last 400 ns of simulation for nCOV-2019, SARS-COV, and extended mutant systems and the last 200 ns for the other mutant systems (Figure 6).
T164 6830-7029 Sentence denotes The DCCM for nCOV-2019 showed a correlation between residues 490–505 (containing α5, L4 and β5 regions) and residues 440–455 (containing α4, L1 and β5 regions) shown in the red rectangle in Figure 6.
T165 7030-7117 Sentence denotes This correlation showed the coordination of these regions for binding ACE2 effectively.
T166 7118-7236 Sentence denotes Another important correlation that appears in the DCCM of nCOV-2019 is between residues 473–481 with residues 482–491.
T167 7237-7338 Sentence denotes These residues are in L3 and β6 regions and their correlation in nCOV-2019 is stronger than SARS-COV.
T168 7339-7450 Sentence denotes This is due to the presence of the β6 strand in nCOV-2019, whereas in SARS-COV these residues all belong to L3.
T169 7451-7640 Sentence denotes This indicates that L3 in nCOV-2019 has evolved from SARS-COV to adopt a new secondary structure, which causes strong correlation and makes the loop act as a recognition region for binding.
T170 7641-7704 Sentence denotes The correlation in L3 is shown as a blue rectangle in Figure 6.
T171 7705-7801 Sentence denotes Some of the mutations disrupted the patterns of correlation and anticorrelation in nCOV-2019-wt.
T172 7802-7890 Sentence denotes Mutation N487A showed a stronger correlation in L3 and β6 strand than the wild-type RBD.
T173 7891-7962 Sentence denotes In mutation E484A, correlation in L3 is stronger than the nCOV-2019-wt.
T174 7963-8009 Sentence denotes DCCM for other mutants are shown in Figure S6.
T175 8010-8181 Sentence denotes It is worth mentioning that mutation F486A disrupts the DCCM of nCOV-2019 by introducing strong correlations in the core region of RBD as well as the extended loop region.
T176 8182-8331 Sentence denotes Residue F486 resides in L3 and plays a crucial role in stabilizing the recognition loop by making a π-stacking interaction with residue Y83A on ACE2.
T177 8332-8423 Sentence denotes Figure 6 DCCM for nCOV-2019, SARS-COV, and mutants with residue numbers of the RBD domain.
T178 8424-8513 Sentence denotes Red boxes show the correlation between α5, L4, and β5 regions and α4, L1, and β5 regions.
T179 8514-8567 Sentence denotes Blue boxes show the correlation in L3 and β6 regions.
T180 8569-8590 Sentence denotes Binding Free Energies
T181 8591-9095 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 9096-9338 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 9339-9643 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 9644-9763 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 9764-9895 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 9896-10152 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 10153-10272 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 10273-10423 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 10424-10513 Sentence denotes A few residues such as E484 and S494 contributed unfavorably to the total binding energy.
T190 10514-10634 Sentence denotes Among all the interface residues K417 had the highest contribution to the total binding energy (−12.34 ± 0.23 kcal/mol).
T191 10635-10805 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 10806-10964 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 10965-11144 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 11145-11365 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 11366-11774 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 11775-11906 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 11907-12114 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 12115-12260 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 12261-12350 Sentence denotes Figure 7 Binding energy decomposition per residue for the RBM of nCOV-2019 and SARS-COV.
T200 12351-12423 Sentence denotes Figure 8 Total free binding energy of SARS-COV, nCOV-2019, and mutants.
T201 12424-12473 Sentence denotes Natural mutants are shown with X at the bar base.
T202 12474-12580 Sentence denotes Binding free energy decomposition to its individual components for all mutants is represented in Table S2.
T203 12581-12767 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 12768-12807 Sentence denotes All variants had similar SASA energies.
T205 12808-12921 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 12922-13159 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 13160-13322 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 13323-13453 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 13454-13551 Sentence denotes Mutants G446A, G447A, and T478I also demonstrated higher total binding affinities than nCOV-2019.
T210 13552-13637 Sentence denotes Other alanine substitutions had similar or lower total binding energy than nCOV-2019.
T211 13638-13753 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 13754-13899 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 13900-14008 Sentence denotes The electrostatic component of binding contributes the most to the low binding affinities for these mutants.
T214 14009-14135 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 14136-14281 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 14282-14323 Sentence denotes The RBD is purple and the ACE2 is yellow.
T217 14324-14501 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 14502-14614 Sentence denotes Most natural mutants exhibited similar binding affinities compared to wild-type nCOV-2019 with a few exceptions.
T219 14615-14786 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 14787-14871 Sentence denotes S494P and A475V showed a slightly lower binding affinity than the wild-type complex.
T221 14872-14945 Sentence denotes Other natural mutants showed binding affinities similar to wild-type RBD.
T222 14946-15145 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.
T223 15147-15207 Sentence denotes Hydrogen Bond, Salt-Bridge, and Hydrophobic Contact Analysis
T224 15208-15512 Sentence denotes Important hydrogen bonds (H-bonds) and salt bridges between nCOV-2019 RBD or SARS-COV RBD and ACE2 for the last 400 ns of trajectory are shown in Table 1. nCOV-2019 RBD makes 10 H-bonds/1 salt bridge with ACE2, whereas SARS-COV makes only 5 H-bonds/1 salt bridge with ACE2 with more than 30% persistence.
T225 15513-15618 Sentence denotes Table 1 H-Bonds and Salt-Bridges between nCOV-2019 and ACE2 and SARS-COV and ACE2 that Persist for >30%a
T226 15619-15679 Sentence denotes # nCOV-2019 ACE2 % occupancy SARS-COV ACE2 % occupancy
T227 15680-15712 Sentence denotes 1 G502 K353 89 Y436 D38 96
T228 15713-15748 Sentence denotes 2 Q493 E35 83 R426 E329 87
T229 15749-15781 Sentence denotes 3 N487 Y83 80 T486 D355 83
T230 15782-15814 Sentence denotes 4 Q498 D38 73 G488 K353 80
T231 15815-15849 Sentence denotes 5 K417 D30 55 N479 K31 52
T232 15850-15882 Sentence denotes 6 T500 D355 53 Y440 H34 47
T233 15883-15908 Sentence denotes 7 Y505 E37 52      
T234 15909-15935 Sentence denotes 8 Q498 K353 49      
T235 15936-15961 Sentence denotes 9 Y449 D38 45      
T236 15962-15989 Sentence denotes 10 G496 K353 37      
T237 15990-16016 Sentence denotes 11 Q493 K31 32      
T238 16017-16049 Sentence denotes a Salt bridge is shown as bold.
T239 16050-16164 Sentence denotes The evolution of the coronavirus from SARS-COV to nCOV-2019 has reshaped the interfacial hydrogen bonds with ACE2.
T240 16165-16233 Sentence denotes G502 in nCOV-2019 has a persistent H-bond with residue K353 on ACE2.
T241 16234-16315 Sentence denotes This residue was G488 in SARS-COV, which also makes the H-bond with K353 on ACE2.
T242 16316-16392 Sentence denotes Q493 in nCOV-2019 makes H-bond with E35 and another H-bond with K31 on ACE2.
T243 16393-16476 Sentence denotes This residue was an N479 in SARS-COV, which only makes one H-bond with K31 on ACE2.
T244 16477-16570 Sentence denotes An important mutation from SARS-COV to nCOV-2019 is residue Q498, which was Y484 in SARS-COV.
T245 16571-16681 Sentence denotes Q498 makes two H-bonds with residues D38 and K353 on ACE2, whereas Y484 in SARS-COV does not make any H-bonds.
T246 16682-16826 Sentence denotes Importantly, a salt bridge between K417 and D30 in the nCOV-2019/ACE2 complex contributes to the total binding energy by −12.34 ± 0.23 kcal/mol.
T247 16827-16937 Sentence denotes This residue is V404 in SARS-COV which is not able to make any salt-bridge and does not make H-bond with ACE2.
T248 16938-17083 Sentence denotes Gao et al.27 used a FEP approach and showed that mutation V404 to K417 lowers the binding energy of nCOV-2019 RBD to ACE2 by −2.2 ± 0.9 kcal/mol.
T249 17084-17175 Sentence denotes A salt bridge between R426 on RBD and E329 on ACE2 stabilizes the complex in SARS-COV/ACE2.
T250 17176-17269 Sentence denotes This residue is N439 in nCOV-2019 which is unable to make salt-bridge with ACE2 residue E329.
T251 17270-17441 Sentence denotes One of the most observed mutations in nCOV-2019 according to the GISAID database is N439K which recovers some of the electrostatic interactions with ACE2 at this position.
T252 17442-17516 Sentence denotes Y436 in SARS-COV and Y449 in nCOV-2019 both make H-bonds with D38 on ACE2.
T253 17517-17643 Sentence denotes The unchanged T486 in SARS-COV corresponds to T500 in nCOV-2019, both of which make consistent H-bonds with ACE2 residue D355.
T254 17644-17746 Sentence denotes Hydrophobic interactions also play an important role in stabilizing the RBD/ACE2 complex in nCOV-2019.
T255 17747-17867 Sentence denotes An important interaction between nCOV-2019 RBD and ACE2 is the π-stacking interaction between F486 (RBD) and Y83 (ACE2).
T256 17868-17970 Sentence denotes This interaction helps in stabilizing L3 in nCOV-2019 compared to SARS-COV where this residue is L472.
T257 17971-18117 Sentence denotes It was observed by Gao et al.26 that mutation L472 to F486 in nCOV-2019 results in a net change in the binding free energy of −1.2 ± 0.2 kcal/mol.
T258 18118-18257 Sentence denotes Other interfacial residues in nCOV-2019 RBD that participate in the hydrophobic interaction with ACE2 are L455, F456, Y473, A475, and Y489.
T259 18258-18347 Sentence denotes It is interesting to note that all these residues except Y489 have mutated from SARS-COV.
T260 18348-18600 Sentence denotes Spinello and co-workers30 performed long-timescale (1μs) simulation of nCOV-2019/ACE2 and SARS-COV ACE2 and found that L3 in nCOV-2019 is more stable due to presence of the β6 strand and existence of two H-bonds in L3 (H-bonds G485-C488 and Q474-G476).
T261 18601-18776 Sentence denotes Importantly, an amino acid insertion in L3 makes this loop longer than L3 in SARS-COV and enables it to act like a recognition loop and make more persistent H-bonds with ACE2.
T262 18777-18937 Sentence denotes L455 in nCOV-2019 RBD is important for hydrophobic interaction with ACE2 and mutation L455A lowers the vdw contribution of binding affinity by about 5 kcal/mol.
T263 18938-19011 Sentence denotes The H-bonds between RBD of nCOV-2019 and SARS-COV are shown in Figure 9A.
T264 19012-19135 Sentence denotes The structural details discussed here are in agreement with other structural studies of the nCOV-2019 RBD/ACE2 complex.4,53
T265 19136-19275 Sentence denotes H-bond analysis was also performed for the mutant systems and the results for H-bonds with more than 40% consistency are shown in Table S3.
T266 19276-19383 Sentence denotes Few of the alanine substitutions increase the number of interfacial H-bonds between nCOV-2019 RBD and ACE2.
T267 19384-19486 Sentence denotes Interestingly, the ala-substitution at Y489A increased the number of H-bonds in the wild-type complex.
T268 19487-19663 Sentence denotes Mutation in some of the residues having consistent H-bonds in the wild type complex such as Q498A and Q493A, stunningly maintain the number of H-bonds in the wild-type complex.
T269 19664-19831 Sentence denotes This indicates that the plasticity in the network of H-bonds in RBM of nCOV-2019 can reshape the network and strengthen other H-bonds upon mutation in these locations.
T270 19832-19913 Sentence denotes However, few mutations decrease the number of H-bonds from the wild-type complex.
T271 19914-20033 Sentence denotes Alanine substitution at residue G502 has a significant effect on the network of H-bonds between nCOV-2019 and SARS-COV.
T272 20034-20125 Sentence denotes This residue locates at the end of L4 loop near two other important residues Q498 and T500.
T273 20126-20177 Sentence denotes This mutation breaks the H-bonds at these residues.
T274 20178-20278 Sentence denotes Mutation K417A decreases the number of H-bonds to only 5 where the H-bond at residue Q498 is broken.
T275 20279-20413 Sentence denotes This indicates the delicate nature of the H-bond from residue Q498 which can easily be broken upon ala-substitution at other residues.
T276 20414-20509 Sentence denotes Furthermore, mutation N487 also decreases the number of H-bonds by breaking the H-bond at Q498.