LitCovid-sentences  

PMC:7441777 / 23528-28835 JSONTXT 10 Projects

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Id Subject Object Predicate Lexical cue
T230 0-6 Sentence denotes 3.2.1.
T231 8-56 Sentence denotes Thermodynamic stability and flexibility analysis
T232 57-341 Sentence denotes The 150 ns production simulations carried out for nine systems (complex of remdesivir, EGCG, TF1, TF2a, TF2b, TF3, hesperidin, myricetin, and quercetagetin with the SARS-CoV-2 RdRp) were stable on the basis of the potential energy and total energy (data not shown) of those complexes.
T233 342-523 Sentence denotes Subsequently, the root-mean-square deviations (RMSDs) of backbone atoms relative to their respective initial positions were calculated for each complex and are shown in Figure 3(A).
T234 524-691 Sentence denotes It is evident from Figure 3(A) that all the nine studied systems drifted from their initial positions during the first 50 ns, and after that, they reached equilibrium.
T235 692-975 Sentence denotes The average RMSD values were estimated to be 2.30 Å, 2.45 Å, 1.87 Å, 2.28 Å, 1.68 Å, 2.47 Å, 1.90 Å, 2.03 Å and 1.88 Å for RdRp/remdesivir, RdRp/EGCG, RdRp/TF3, RdRp/TF2b, RdRp/TF2a, RdRp/myricetin, RdRp/quercetagetin, RdRp/hesperidin, and RdRp/TF1 complexes, respectively (Table 3).
T236 976-1077 Sentence denotes The least deviation was observed for RdRp/TF2a, while RdRp/myricetin displayed the highest deviation.
T237 1078-1299 Sentence denotes We also investigated structural variations in the binding site, including all amino acids that fall within a radius of 5 Å from the inhibitor, and the same trend was observed (Figure S2A in the Supplementary Information).
T238 1300-1358 Sentence denotes Overall, this suggests the convergence of our simulations.
T239 1359-1582 Sentence denotes Figure 3. (A) Time evolution of root-mean-square deviations (RMSDs) of backbone atoms and (B) the root-mean-square fluctuations (RMSFs) of Cα atoms of nine complexes relative to their respective energy minimized structure.
T240 1583-1591 Sentence denotes Table 3.
T241 1593-1712 Sentence denotes The average backbone RMSD, radius of gyration (RoG), and solvent accessible surface area (SASA) for all nine complexes.
T242 1713-1781 Sentence denotes The data are reported as average ± standard error of the mean (SEM).
T243 1782-1818 Sentence denotes System RMSD (Å) RoG (Å) SASA (Å2)
T244 1819-1879 Sentence denotes RdRp/Remdesivir 2.30 ± 0.03 29.96 ± 0.02 34973.20 ± 91.56
T245 1880-1934 Sentence denotes RdRp/EGCG 2.45 ± 0.05 29.52 ± 0.06 35026.03 ± 63.52
T246 1935-1988 Sentence denotes RdRp/TF3 1.87 ± 0.02 29.60 ± 0.01 34080.16 ± 53.41
T247 1989-2043 Sentence denotes RdRp/TF2b 2.28 ± 0.01 29.86 ± 0.02 35462.92 ± 50.40
T248 2044-2099 Sentence denotes RdRp/TF2a 1.68 ± 0.02 29.75 ± 0.02 34312.55 ± 112.89
T249 2100-2160 Sentence denotes RdRp/Myricetin 2.47 ± 0.03 29.88 ± 0.01 35395.35 ± 104.67
T250 2161-2224 Sentence denotes RdRp/Quercetagetin 1.90 ± 0.03 29.84 ± 0.01 34618.65 ± 51.25
T251 2225-2285 Sentence denotes RdRp/Hesperidin 2.03 ± 0.04 29.74 ± 0.02 34554.08 ± 47.25
T252 2286-2570 Sentence denotes RdRp/TF1 1.88 ± 0.03 29.86 ± 0.01 34420.69 ± 56.90 Next, we investigated the structural stability of remdesivir and eight polyphenols by estimating the temporal RMSDs of heavy atoms relative to their respective initial coordinates (see Figure S2B in the Supplementary Information).
T253 2571-2724 Sentence denotes It is evident from Figure S2B that EGCG, myricetin, quercetagetin, TF1, TF3 displayed a rigid behavior in the bound form with an average RMSD of < 1.0 Å.
T254 2725-2887 Sentence denotes However, remdesivir, TF2a, TF2b and hesperidin showed higher fluctuations as compared to the abovementioned polyphenols, and an average RMSD of > 2.0 Å was noted.
T255 2888-3042 Sentence denotes To identify the regions which are flexible, the root-mean-square fluctuations (RMSFs) of Cα atoms of each residue are calculated and shown in Figure 3(B).
T256 3043-3214 Sentence denotes From this analysis, we can get a better insight into what extent the binding of remdesivir and natural polyphenols affects the residual flexibility of RdRp (mainly Nsp12).
T257 3215-3309 Sentence denotes Figure 3(B) indicates that RdRp/remdesivir and RdRp-polyphenols shared a similar RMSF pattern.
T258 3310-3425 Sentence denotes Notable dynamic fluctuations were located in the non-active site domain, including both N-terminals and C-terminal.
T259 3426-3559 Sentence denotes Regions around Asn150, Asp260, Arg305, Asn360, and Phe440 are found to be more flexible compared to the other area for all complexes.
T260 3560-3884 Sentence denotes The binding pocket residues, such as Asp452, Lys545, Lys551, Tyr455, Arg553, Ala554, Arg555, Thr556, Asp618, Tyr619, pro620, Lys621, Cys622, Asp623 Arg624, Asn691, Asp760, Asp761, Phe793, Met794, Ser795, Lys798, Trp800, Glu811, Phe812, and Ser814 exhibited considerably low fluctuations for all the RdRp-inhibitor complexes.
T261 3885-4028 Sentence denotes In the case of RdRp/TF3 and RdRp/TF2a, the binding site residues displayed lesser fluctuations compared to the other RdRp-polyphenol complexes.
T262 4029-4133 Sentence denotes This suggests that TF3 and TF2a are likely to be bound to RdRp more strongly than the other polyphenols.
T263 4134-4325 Sentence denotes Since the radius of gyration (RoG) helps us to understand the protein structural compactness, RoG of each complex was monitored and represented in Figure S3A in the Supplementary Information.
T264 4326-4566 Sentence denotes The average values of RoG are 29.96 Å, 29.52 Å, 29.60 Å, 29.86 Å, 29.75 Å, 29.88 Å, 29.84 Å, 29.74 Å and 29.86 Å for RdRp complexed with remdesivir, EGCG, TF3, TF2b, TF2a, myricetin, quercetagetin, hesperidin and TF1 respectively (Table 3).
T265 4567-4651 Sentence denotes This suggests that the structural compactness remained unchanged during simulations.
T266 4652-4846 Sentence denotes Finally, the solvent-accessible surface area (SASA) was also explored, and the time evolution of SASA for four RdRp-polyphenol complexes are shown in Figure S3B in the Supplementary Information.
T267 4847-4898 Sentence denotes The average values of SASA are reported in Table 3.
T268 4899-5010 Sentence denotes Binding of an inhibitor to the substrate changes SASA and sometimes could greatly affect the protein structure.
T269 5011-5135 Sentence denotes Here, a relatively higher SASA value was obtained for RdRp/TF2b (35462.9 Å2) compared to the other RdRp/inhibitor complexes.
T270 5136-5213 Sentence denotes On the other hand, the lowest SASA value was noted for RdRp/TF3 (34080.2 Å2).
T271 5214-5307 Sentence denotes Thus, it can be suggested that the binding of TF3 could potentially reduce protein expansion.