LitCovid-sentences  

PMC:7441777 / 32895-40997 JSONTXT 8 Projects

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Id Subject Object Predicate Lexical cue
T307 0-6 Sentence denotes 3.2.3.
T308 8-50 Sentence denotes Essential residues for polyphenols binding
T309 51-260 Sentence denotes Further, to gain a deeper insight into the best four RdRp/polyphenols and remdesivir interaction pattern, the total binding free energy was decomposed into polyphenols-residue pair based on the MM-GBSA scheme.
T310 261-451 Sentence denotes The approach of per-residue based contributions is useful to determine the binding mechanisms of an inhibitor at an atomistic level, and it also reveals the individual residue contributions.
T311 452-580 Sentence denotes The different energy contributions from the backbone and side-chain of each residue are shown in Figure 5 and listed in Table 5.
T312 581-590 Sentence denotes Figure 5.
T313 592-738 Sentence denotes Decomposition of the binding free energy into contributions from individual residues for RdRp complexed with remdesivir, EGCG, TF3, TF2b and TF2a.
T314 739-747 Sentence denotes Table 5.
T315 749-885 Sentence denotes Per-residue based decomposition of binding free energy for the complex of remdesivir, EGCG, TF3, TF2a and TF2b with the SARS-CoV-2 RdRp.
T316 886-949 Sentence denotes Residue TvdW Telec Tpol Tnp Tside_chain Tbackbone Ttotal
T317 950-965 Sentence denotes RdRp/Remdesivir
T318 966-1021 Sentence denotes Asp761 1.05 −21.73 18.81 −0.14 −1.82 −0.19 −2.01
T319 1022-1075 Sentence denotes Lys798 −2.74 −4.28 5.74 −0.47 −1.76 0.01 −1.75
T320 1076-1130 Sentence denotes Pro620 −1.42 −1.15 1.16 −0.18 −1.26 −0.33 −1.59
T321 1131-1185 Sentence denotes Asp760 −0.57 −4.27 4.24 −0.12 −0.20 −0.52 −0.72
T322 1186-1239 Sentence denotes Arg553 −2.07 −3.71 5.61 −0.51 −0.76 0.08 −0.68
T323 1240-1249 Sentence denotes RdRp/EGCG
T324 1250-1303 Sentence denotes Asp452 1.65 −16.48 9.85 −0.08 −5.15 0.09 −5.06
T325 1304-1357 Sentence denotes Arg553 −3.83 −4.84 6.59 −0.59 −2.68 0.01 −2.67
T326 1358-1412 Sentence denotes Pro620 −1.64 −0.41 0.51 −0.33 −1.62 −0.25 −1.87
T327 1413-1466 Sentence denotes Asp618 0.49 −8.14 6.66 −0.09 −1.13 −0.05 −1.08
T328 1467-1521 Sentence denotes Lys621 −2.26 −5.12 6.92 −0.50 −0.87 −0.09 −0.96
T329 1522-1530 Sentence denotes RdRp/TF3
T330 1531-1586 Sentence denotes Asp761 2.52 −30.13 22.11 −0.25 −5.54 −0.21 −5.75
T331 1587-1643 Sentence denotes Arg836 −0.83 −14.95 12.29 −0.37 −3.85 −0.01 −3.86
T332 1644-1698 Sentence denotes Arg555 −5.80 −4.00 7.29 −0.70 −2.98 −0.23 −3.21
T333 1699-1753 Sentence denotes Thr556 −0.20 −3.96 2.44 −0.13 −0.21 −1.64 −1.85
T334 1754-1808 Sentence denotes Ile548 −1.03 −0.08 0.12 −0.13 −0.65 −0.47 −1.12
T335 1809-1862 Sentence denotes Ser814 −1.67 0.09 0.78 −0.08 −0.48 −0.40 −0.88
T336 1863-1917 Sentence denotes Val557 −0.65 −0.16 0.17 −0.24 −0.65 −0.23 −0.88
T337 1918-1927 Sentence denotes RdRp/TF2b
T338 1928-1982 Sentence denotes His816 −3.00 −0.81 1.69 −0.32 −1.63 −0.81 −2.44
T339 1983-2037 Sentence denotes Asp833 −1.29 −0.23 0.46 −0.18 −0.21 −1.03 −1.24
T340 2038-2092 Sentence denotes Tyr877 −0.92 −2.06 2.06 −0.27 −0.43 −0.76 −1.19
T341 2093-2145 Sentence denotes Glu811 0.22 −9.24 8.11 −0.13 −2.07 1.03 −1.04
T342 2146-2200 Sentence denotes His810 −1.88 −0.41 1.66 −0.34 −0.10 −0.85 −0.95
T343 2201-2255 Sentence denotes Tyr831 −1.51 −0.36 1.19 −0.13 −0.21 −0.60 −0.81
T344 2256-2310 Sentence denotes Asn815 −0.60 −0.27 0.09 −0.01 −0.25 −0.54 −0.79
T345 2311-2320 Sentence denotes RdRp/TF2a
T346 2321-2376 Sentence denotes Asp618 2.63 −20.71 13.40 −0.17 −4.84 −0.01 −4.85
T347 2377-2431 Sentence denotes Arg553 −3.80 −6.52 7.55 −0.69 −2.68 −0.78 −3.46
T348 2432-2486 Sentence denotes Lys551 −2.23 −0.80 2.23 −0.45 −0.84 −0.41 −1.25
T349 2487-2541 Sentence denotes Arg555 −1.33 −0.62 1.05 −0.27 −1.12 −0.05 −1.17
T350 2542-2824 Sentence denotes Glu167 0.42 −6.82 5.92 −0.12 −0.61 0.01 −0.60 As shown in Figure 5, it was observed that residues favoring the binding of the polyphenols with RdRp include Asp452, Arg553, Arg555, Val557, Asp618, Pro620, Lys621, Asp623, Arg624, Asp760, Asp761, and Glu811, Asp833, and Arg836.
T351 2825-2949 Sentence denotes Most of these residues are located in the binding site of RdRp and can form direct contacts with polyphenols and remdesivir.
T352 2950-3326 Sentence denotes Figure 5 shows that amino acids Pro620, Asp761 and Lys798 for RdRp/remdesivir; Asp452, Arg553, Pro620 and Lys621 for RdRp/EGCG; Ile548, Arg555, Thr556, Asp761 and Arg836 for RdRp/TF3; Glu811, His816, Asp833 and Tyr877 for RdRp/TF2b; Lys551, Arg553, Arg555 and Asp618 for RdRp/TF2a contributed more favorably towards the binding by contributing more than −1.0 kcal/mol in size.
T353 3327-3507 Sentence denotes To complement the energetic analysis, we performed MD trajectory-based hydrogen bond (h-bond) analysis for all five complexes, and the h-bonds with occupancy are listed in Table 6.
T354 3508-3616 Sentence denotes The h-bonds were determined by setting the acceptor-donor distance of ≤ 3.5 Å, and the angle cut off ≥ 1200.
T355 3617-3681 Sentence denotes Important h-bonds between RdRp-inhibitors are shown in Figure 6.
T356 3682-3805 Sentence denotes In the case of RdRp/remdesivir, key residues involved in the hydrogen bonding are Asp761, Asp760, and Ser759, respectively.
T357 3806-3963 Sentence denotes Asp760 is found to form two h-bonds with remdesivir (Asp760@OD2 - Lig@O7, Asp760@OD2 - Lig@O6) with an occupancy of more than 15% (see Table 6 and Figure 6).
T358 3964-4096 Sentence denotes In the case of RdRp/EGCG, both Asp618 and Asp760 form two h-bonds with the ligand with an occupancy in the range of 16.09 to 30.17%.
T359 4097-4344 Sentence denotes On the other hand, Asp761 form an h-bond with TF3 (Asp761@OD1 - Lig@O11) with an occupancy of 69.84%, while Arg836 forms two h-bonds with the ligand (Arg836@NH2 - Lig@O14, Arg836@NE - Lig@O14) with an occupancy of 52.66%, and 48.70%, respectively.
T360 4345-4497 Sentence denotes Glu811, Thr556 and Asp761 also formed h-bonds with the ligand during our simulations with an occupancy varying in the range of 44% to 58% (see Table 6).
T361 4498-4679 Sentence denotes In the case of RdRp/TF2b, Glu811 is found to form two strong h–bonds with the ligand (Glu811@OE1 – Lig@O7, Glu811@OE2 – Lig@O7) with an occupancy of 22.45% and 18.89%, respectively.
T362 4680-4849 Sentence denotes On the other hand, it can be observed from Table 6 that Pro832 and Tyr877 form strong h-bonds (Pro832@O -Lig@O8 and Lig@O10 -Tyr877@OH) with increased occupancy (> 24%).
T363 4850-5040 Sentence denotes Finally, in the case of RdRp/TF2a, Asp618 is found to form two strong h-bonds with the TF2a (Asp618@OD1 – Lig@O10, Asp618@OD1 – Lig@O11) with an occupancy of 38.68% and 38.38%, respectively.
T364 5041-5117 Sentence denotes Asp760 also forms a h-bond (Asp760@O – Lig@O11) with an occupancy of 20.83%.
T365 5118-5127 Sentence denotes Figure 6.
T366 5129-5191 Sentence denotes Five main hydrogen bond interactions between ligands and RdRp.
T367 5192-5200 Sentence denotes Table 6.
T368 5202-5415 Sentence denotes Main hydrogen bond interactions formed by RdRp with remdesivir and polyphenols along with the corresponding average distance and percentage of occupancy determined using the trajectories of production simulations.
T369 5416-5437 Sentence denotes Acceptor Donor Avg.
T370 5438-5465 Sentence denotes Distance (Å) Occupancy (%)
T371 5466-5481 Sentence denotes RdRp/Remdesivir
T372 5482-5513 Sentence denotes Asp760@OD2 Lig@O7 2.66 19.46
T373 5514-5545 Sentence denotes Asp761@OD1 Lig@O7 2.65 17.70
T374 5546-5577 Sentence denotes Asp761@OD2 Lig@O6 2.63 16.86
T375 5578-5609 Sentence denotes Asp760@OD2 Lig@O6 2.65 16.65
T376 5610-5640 Sentence denotes Lig@O6 Ser759@OG 2.80 11.63
T377 5641-5672 Sentence denotes Asp760@OD1 Lig@O7 2.66 10.59
T378 5673-5682 Sentence denotes RdRp/EGCG
T379 5683-5714 Sentence denotes Asp618@OD1 Lig@O5 2.61 30.13
T380 5715-5746 Sentence denotes Asp618@OD1 Lig@O6 2.61 29.28
T381 5747-5778 Sentence denotes Asp618@OD2 Lig@O5 2.61 18.25
T382 5779-5810 Sentence denotes Asp618@OD2 Lig@O6 2.61 17.38
T383 5811-5842 Sentence denotes Asp760@OD1 Lig@O5 2.63 16.09
T384 5843-5874 Sentence denotes Tyr455@OH Lig@O11 2.83 10.97
T385 5875-5883 Sentence denotes RdRp/TF3
T386 5884-5916 Sentence denotes Asp761@OD1 Lig@O11 2.61 69.84
T387 5917-5947 Sentence denotes Glu811@O Lig@O10 2.76 58.43
T388 5948-5977 Sentence denotes Thr556@O Lig@O3 2.72 56.95
T389 5978-6010 Sentence denotes Lig@O14 Arg836@NH2 2.83 52.66
T390 6011-6042 Sentence denotes Lig@O14 Arg836@NE 2.86 48.70
T391 6043-6075 Sentence denotes Asp761@OD2 Lig@O20 2.62 44.51
T392 6076-6085 Sentence denotes RdRp/TF2b
T393 6086-6115 Sentence denotes Pro832@O Lig@O8 2.77 26.31
T394 6116-6147 Sentence denotes Lig@O11 Tyr877@OH 2.75 24.39
T395 6148-6179 Sentence denotes Glu811@OE1 Lig@O7 2.65 22.45
T396 6180-6211 Sentence denotes Glu811@OE2 Lig@O7 2.65 18.89
T397 6212-6243 Sentence denotes Asp833@OD2 Lig@O8 2.65 12.01
T398 6244-6275 Sentence denotes Asn874@OD1 Lig@O11 2.68 8.58
T399 6276-6285 Sentence denotes RdRp/TF2a
T400 6286-6318 Sentence denotes Asp618@OD1 Lig@O10 2.59 38.68
T401 6319-6351 Sentence denotes Asp618@OD1 Lig@O11 2.62 38.38
T402 6352-6382 Sentence denotes Asp760@O Lig@O11 2.70 20.83
T403 6383-6415 Sentence denotes Asp618@OD2 Lig@O11 2.62 16.59
T404 6416-6448 Sentence denotes Asp618@OD2 Lig@O10 2.58 16.49
T405 6449-6704 Sentence denotes Asp618@OD1 Lig@O15 2.67 16.37 Finally, we supplemented the above results by analyzing the final conformation of each production simulation with the help of 2D LigPlot+ software, and different h-bonds and hydrophobic interactions were shown in Figure 7.
T406 6705-6827 Sentence denotes Hydrogen bonds are depicted in green dotted lines, while red semicircle residues are involved in hydrophobic interactions.
T407 6828-6993 Sentence denotes For the RdRp/remdesivir complex, Figure 7(A) displayed nine hydrophobic interactions with Lys545, Ala547, Ser549, Arg553, Val557, Asp684, Ser759, Ser814, and Arg836.
T408 6994-7107 Sentence denotes This large number of interactions account for the high stability and good binding affinity of remdesivir to RdRp.
T409 7108-7204 Sentence denotes EGCG formed hydrophobic interactions with Lys551, Ala554, Arg553, Arg624, Pro620, (Figure 7(B)).
T410 7205-7366 Sentence denotes In the case of TF3, eight hydrophobic interactions with His439, Ile548, Ser814, Phe812, Val557, Ser549, Tyr619 and Arg555 were formed as revealed by Figure 7(C).
T411 7367-7510 Sentence denotes Figure 7(D) shows that seven hydrophobic interactions with Asp833, His816, Pro832, Gln815, His872, His810 and Ser434 were formed for RdRp/TF2b.
T412 7511-7616 Sentence denotes Finally, Figure 7(E) shows that RdRp/TF2a formed hydrophobic interactions with Arg555, Ala554 and Lys551.
T413 7617-7783 Sentence denotes Overall, TF3 has a higher binding affinity toward RdRp compared to the other polyphenols due to a larger number of stable hydrogen bonds and hydrophobic interactions.
T414 7784-7793 Sentence denotes Figure 7.
T415 7795-7918 Sentence denotes The RdRp-ligands interaction profile for (A) RdRp/remdesivir, (B) RdRp/EGCG, (C) RdRp/TF3, (D) RdRp/TF2b and (E) RdRp/TF2a.
T416 7919-7980 Sentence denotes The polyphenols and remdesivir are shown in balls and sticks.
T417 7981-8102 Sentence denotes Hydrogen bonds are depicted in green dotted lines, and red semicircles residues are involved in hydrophobic interactions.