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PMC:7605337 / 13003-19979 JSONTXT

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LitCovid-PD-FMA-UBERON

Id Subject Object Predicate Lexical cue fma_id
T44 311-318 Body_part denotes protein http://purl.org/sig/ont/fma/fma67257
T45 454-461 Body_part denotes alanine http://purl.org/sig/ont/fma/fma82749
T46 1841-1849 Body_part denotes backbone http://purl.org/sig/ont/fma/fma13478
T47 2203-2211 Body_part denotes backbone http://purl.org/sig/ont/fma/fma13478
T48 5215-5223 Body_part denotes backbone http://purl.org/sig/ont/fma/fma13478

LitCovid-PD-MONDO

Id Subject Object Predicate Lexical cue mondo_id
T97 40-49 Disease denotes nCOV-2019 http://purl.obolibrary.org/obo/MONDO_0100096
T98 107-111 Disease denotes SARS http://purl.obolibrary.org/obo/MONDO_0005091
T99 217-226 Disease denotes nCOV-2019 http://purl.obolibrary.org/obo/MONDO_0100096
T100 264-268 Disease denotes SARS http://purl.obolibrary.org/obo/MONDO_0005091
T101 422-431 Disease denotes nCOV-2019 http://purl.obolibrary.org/obo/MONDO_0100096
T102 433-437 Disease denotes SARS http://purl.obolibrary.org/obo/MONDO_0005091
T103 479-488 Disease denotes nCOV-2019 http://purl.obolibrary.org/obo/MONDO_0100096
T104 1151-1160 Disease denotes nCOV-2019 http://purl.obolibrary.org/obo/MONDO_0100096
T105 3031-3035 Disease denotes SARS http://purl.obolibrary.org/obo/MONDO_0005091
T106 3044-3053 Disease denotes nCOV-2019 http://purl.obolibrary.org/obo/MONDO_0100096
T107 3542-3546 Disease denotes SARS http://purl.obolibrary.org/obo/MONDO_0005091
T108 3552-3561 Disease denotes nCOV-2019 http://purl.obolibrary.org/obo/MONDO_0100096
T109 3920-3924 Disease denotes SARS http://purl.obolibrary.org/obo/MONDO_0005091
T110 3930-3939 Disease denotes nCOV-2019 http://purl.obolibrary.org/obo/MONDO_0100096
T111 5306-5310 Disease denotes SARS http://purl.obolibrary.org/obo/MONDO_0005091
T112 5319-5328 Disease denotes nCOV-2019 http://purl.obolibrary.org/obo/MONDO_0100096
T113 5813-5817 Disease denotes SARS http://purl.obolibrary.org/obo/MONDO_0005091
T114 5826-5835 Disease denotes nCOV-2019 http://purl.obolibrary.org/obo/MONDO_0100096

LitCovid-PD-CLO

Id Subject Object Predicate Lexical cue
T87 0-2 http://purl.obolibrary.org/obo/CLO_0007622 denotes MD
T88 129-134 http://purl.obolibrary.org/obo/NCBITaxon_9606 denotes human
T89 196-198 http://purl.obolibrary.org/obo/CLO_0001302 denotes 34
T90 527-529 http://purl.obolibrary.org/obo/CLO_0001000 denotes 35
T91 530-531 http://purl.obolibrary.org/obo/CLO_0001020 denotes A
T92 649-650 http://purl.obolibrary.org/obo/CLO_0001020 denotes A
T93 1469-1470 http://purl.obolibrary.org/obo/CLO_0001020 denotes a
T94 1655-1656 http://purl.obolibrary.org/obo/CLO_0001020 denotes a
T95 1729-1730 http://purl.obolibrary.org/obo/CLO_0001020 denotes a
T96 1735-1737 http://purl.obolibrary.org/obo/CLO_0008491 denotes ps
T97 1889-1890 http://purl.obolibrary.org/obo/CLO_0001020 denotes A
T98 2052-2053 http://purl.obolibrary.org/obo/CLO_0001020 denotes a
T99 2103-2104 http://purl.obolibrary.org/obo/CLO_0001020 denotes a
T100 2506-2508 http://purl.obolibrary.org/obo/CLO_0007622 denotes MD
T101 2641-2642 http://purl.obolibrary.org/obo/CLO_0001020 denotes a
T102 2690-2694 http://purl.obolibrary.org/obo/CLO_0001757 denotes at 1
T103 2743-2744 http://purl.obolibrary.org/obo/CLO_0001020 denotes a
T104 2784-2785 http://purl.obolibrary.org/obo/CLO_0001020 denotes a
T105 2811-2813 http://purl.obolibrary.org/obo/CLO_0008491 denotes ps
T106 2987-2989 http://purl.obolibrary.org/obo/CLO_0053794 denotes 41
T107 3100-3103 http://purl.obolibrary.org/obo/CLO_0001562 denotes a 2
T108 3100-3103 http://purl.obolibrary.org/obo/CLO_0001563 denotes a 2
T109 3355-3356 http://purl.obolibrary.org/obo/CLO_0001020 denotes a
T110 3842-3843 http://purl.obolibrary.org/obo/CLO_0001020 denotes a
T111 4249-4250 http://purl.obolibrary.org/obo/CLO_0001020 denotes a
T112 4530-4532 http://purl.obolibrary.org/obo/CLO_0007622 denotes MD
T113 4659-4662 http://purl.obolibrary.org/obo/CLO_0003078 denotes FEL
T114 5236-5237 http://purl.obolibrary.org/obo/CLO_0001020 denotes a
T115 5410-5411 http://purl.obolibrary.org/obo/CLO_0001020 denotes a
T116 5416-5418 http://purl.obolibrary.org/obo/CLO_0008491 denotes ps
T117 6041-6042 http://purl.obolibrary.org/obo/CLO_0001020 denotes a
T118 6251-6252 http://purl.obolibrary.org/obo/CLO_0001020 denotes a
T119 6260-6276 http://purl.obolibrary.org/obo/GO_0043235 denotes receptor complex
T120 6302-6305 http://purl.obolibrary.org/obo/CLO_0001302 denotes 3 4
T121 6622-6624 http://purl.obolibrary.org/obo/CLO_0001382 denotes 48
T122 6790-6791 http://purl.obolibrary.org/obo/CLO_0001020 denotes a

LitCovid-PD-CHEBI

Id Subject Object Predicate Lexical cue chebi_id
T49 0-2 Chemical denotes MD http://purl.obolibrary.org/obo/CHEBI_74699
T50 311-318 Chemical denotes protein http://purl.obolibrary.org/obo/CHEBI_36080
T51 454-461 Chemical denotes alanine http://purl.obolibrary.org/obo/CHEBI_16449
T52 538-543 Chemical denotes water http://purl.obolibrary.org/obo/CHEBI_15377
T53 567-574 Chemical denotes solvent http://purl.obolibrary.org/obo/CHEBI_46787
T54 663-667 Chemical denotes ions http://purl.obolibrary.org/obo/CHEBI_24870
T55 879-884 Chemical denotes atoms http://purl.obolibrary.org/obo/CHEBI_33250
T56 1124-1127 Chemical denotes Cys http://purl.obolibrary.org/obo/CHEBI_15356|http://purl.obolibrary.org/obo/CHEBI_17561|http://purl.obolibrary.org/obo/CHEBI_29950
T59 1198-1207 Chemical denotes disulfide http://purl.obolibrary.org/obo/CHEBI_48343
T60 1450-1458 Chemical denotes hydrogen http://purl.obolibrary.org/obo/CHEBI_49637
T61 1459-1464 Chemical denotes atoms http://purl.obolibrary.org/obo/CHEBI_33250
T62 1865-1870 Chemical denotes atoms http://purl.obolibrary.org/obo/CHEBI_33250
T63 2227-2232 Chemical denotes atoms http://purl.obolibrary.org/obo/CHEBI_33250
T64 2506-2508 Chemical denotes MD http://purl.obolibrary.org/obo/CHEBI_74699
T65 3680-3683 Chemical denotes PCA http://purl.obolibrary.org/obo/CHEBI_36751|http://purl.obolibrary.org/obo/CHEBI_62248
T67 4105-4110 Chemical denotes atoms http://purl.obolibrary.org/obo/CHEBI_33250
T68 4530-4532 Chemical denotes MD http://purl.obolibrary.org/obo/CHEBI_74699
T69 5227-5232 Chemical denotes atoms http://purl.obolibrary.org/obo/CHEBI_33250
T70 5434-5442 Chemical denotes Hydrogen http://purl.obolibrary.org/obo/CHEBI_18276
T71 5538-5543 Chemical denotes donor http://purl.obolibrary.org/obo/CHEBI_17891
T72 5548-5556 Chemical denotes acceptor http://purl.obolibrary.org/obo/CHEBI_15339
T73 6253-6259 Chemical denotes ligand http://purl.obolibrary.org/obo/CHEBI_52214
T74 6814-6821 Chemical denotes solvent http://purl.obolibrary.org/obo/CHEBI_46787
T75 6909-6916 Chemical denotes solvent http://purl.obolibrary.org/obo/CHEBI_46787

LitCovid-PD-GO-BP

Id Subject Object Predicate Lexical cue
T4 983-996 http://purl.obolibrary.org/obo/GO_0070085 denotes glycosylation
T5 3768-3781 http://purl.obolibrary.org/obo/GO_0006412 denotes translational

LitCovid-sentences

Id Subject Object Predicate Lexical cue
T64 0-14 Sentence denotes MD Simulations
T65 15-148 Sentence denotes The crystal structure of nCOV-2019 in the complex with hACE2 (pdb id:6M0J)17 as well as the SARS-COV complex with human ACE2 (pdb id:
T66 149-305 Sentence denotes 6ACJ)33 were obtained from RCSB (www.rcsb.org).34 The RBD domain of nCOV-2019 comprises 194 residues (333–526) and SARS-COV includes 190 residues (323–512).
T67 306-392 Sentence denotes ACE2 protein contains 597 residues (19–615) in the complex structure for both systems.
T68 393-648 Sentence denotes All the structures including nCOV-2019, SARS-COV, and all 21 alanine substitutions of nCOV-2019 were prepared and solvated in GROMACS.35 A TIP3P water model was used for the solvent and Param99SB-ILDN AMBER force field36,37 was used for all the complexes.
T69 649-842 Sentence denotes A few counter ions were added to each system to neutralize the charges on the RBD and ACE2 as the PBSA method for binding energy calculation is known to be problematic with high ionic strength.
T70 843-885 Sentence denotes Each system contained about 260,000 atoms.
T71 886-978 Sentence denotes It is important to note that, none of the RBD/ACE2 complexes studied here were glycosylated.
T72 979-1098 Sentence denotes The glycosylation sites on RBD are far from the binding interface and do not interfere with the binding of RBD to ACE2.
T73 1099-1279 Sentence denotes Moreover, there are nine Cys residues at the RBD of nCOV-2019 and eight of them form four pairs of disulfide bonds (Cys336-Cys361, Cys379-Cys432, Cys391-Cys525, and Cys480-Cys488).
T74 1280-1372 Sentence denotes In total, 5000 steps of energy minimizations were done using the steepest descent algorithm.
T75 1373-1527 Sentence denotes In all steps, the LINCS algorithm was used to constrain all bonds containing hydrogen atoms and a time step of 2 fs was used as the integration time step.
T76 1528-1586 Sentence denotes Equilibration of all systems was performed in three steps.
T77 1587-1963 Sentence denotes In the first step, 100,000 steps of simulation were performed using a velocity-rescaling thermostat to maintain the temperature at 310 K with a 0.1 ps coupling constant in an NVT ensemble under periodic boundary conditions and harmonic restraints on the backbone and side-chain atoms of the complex.38 A velocity rescaling thermostat was used in all other steps of simulation.
T78 1964-2284 Sentence denotes In the next step, we performed 300,000 steps in the isothermal-isobaric NPT ensemble at a temperature of 310 K and pressure of 1 bar using a Berendsen barostat.39 This was done through decreasing the force constant of the restraint on the backbone and side-chain atoms of the complex from 1000 to 100 and finally to 10 .
T79 2285-2405 Sentence denotes The Berendsen barostat was only used for the equilibration step because of its usefulness in rapidly correcting density.
T80 2406-2543 Sentence denotes In the next step, the restraints were removed, and the systems were subjected to 1,000,000 steps of MD simulation under the NPT ensemble.
T81 2544-2814 Sentence denotes In the production run, harmonic restraints were removed and all the systems were simulated using a NPT ensemble where the pressure was maintained at 1 bar using the Parrinello-Rahman barostat40 with a compressibility of 4.5 × 10–5bar–1 and a coupling constant of 0.5 ps.
T82 2815-3317 Sentence denotes It is important to note that the Berendsen barostat was only used for the equilibration step as it was shown that this barostat can cause unrealistic temperature gradients.41 The production run lasted for 500 ns for SARS-COV and nCOV-2019 complexes and 300 ns for all the mutants with a 2 fs timestep and the particle-mesh Ewald42 for long range electrostatic interactions using the GROMACS 2018.3 package.43 All mutant systems were constructed as described before and ran for 300 ns of production run.
T83 3318-3425 Sentence denotes In addition, the simulation time for a few mutants (Y449A, T478I, Y489A, and S494P) was extended to 500 ns.
T84 3427-3467 Sentence denotes Gibbs Free Energy and Correlated Motions
T85 3468-3874 Sentence denotes The last 400 ns of simulation was used to explore the dominant motions in SARS-COV, nCOV-2019 and the mutations with extended simulation, and last 200 ns for all other mutants using principal component analysis (PCA) as part of the quasiharmonic analysis method.44 For this method the rotational and translational motions of RBD of all systems were eliminated by fitting to a reference (crystal) structure.
T86 3875-4118 Sentence denotes Next, 4000 snapshots from the last 400 ns of SARS-COV, nCOV-2019 and mutations with extended simulation time, and 2000 snapshots from last 200 ns of all other mutant systems were taken to generate the covariance matrix between Cα atoms of RBD.
T87 4119-4205 Sentence denotes In the mutant systems with production run, the last 400 ns was used for this analysis.
T88 4206-4539 Sentence denotes Diagonalization of this matrix resulted in a diagonal matrix of eigenvalues and their corresponding eigenvectors.43,45 The first eigenvector which indicate the first principal component was used to visualize the dominant global motions of all complexes through porcupine plots using the (PorcupinePlot.tcl) script in visual MD (VMD).
T89 4540-4642 Sentence denotes The principal components were used to calculate and plot the approximate free energy landscape (aFEL).
T90 4643-5003 Sentence denotes We refer to the FEL produced by this approach to be approximate in that the ensemble with respect to the first few PC’s (lowest frequency quasiharmonic modes) is not close to convergence, but the analysis can still provide valuable information and insight. g_sham, g_covar, and g_anaeig functions in GROMACS35 were used to obtain principal components and aFEL.
T91 5004-5255 Sentence denotes The dynamic cross-correlation maps (DCCM) were obtained using the MD_TASK package to identify the correlated motions of RBD residues.46 In DCCM, the cross-correlation matrix Cij is obtained from displacement of backbone Cα atoms at a time interval Δt.
T92 5256-5433 Sentence denotes The DCCM was constructed using the last 400 ns of SARS-COV and nCOV-2019 and the extended mutant systems and last 200 ns of all other mutant systems with a 100 ps time interval.
T93 5434-5565 Sentence denotes Hydrogen bonds were analyzed in VMD where the distance cutoff was 3.2Å and the angle cutoff between the donor and acceptor was 30°.
T94 5567-5649 Sentence denotes Binding Free Energy from Molecular Mechanics Poisson-Boltzmann Surface Area Method
T95 5650-6025 Sentence denotes The molecular mechanics Poisson-Boltzmann surface area (MMPBSA) method was applied to calculate the binding energy between RBD and ACE2 in all complexes.47,48 For SARS-COV and nCOV-2019, 200 snapshots of the last 400 ns and for the mutant systems and 100 snapshots of the last 200 ns simulation were used for the calculation of binding free energies with an interval of 2 ns.
T96 6026-6223 Sentence denotes Simulation for a few mutant systems (Y449A, T478I, Y489A, and S494P) was extended to 400 ns, and the binding energies were calculated for the last 400 ns to assess the convergence of free energies.
T97 6224-6307 Sentence denotes The binding free energy of a ligand–receptor complex can be calculated as:1 2 3 4 5
T98 6308-6515 Sentence denotes In these equations, ΔEMM, ΔGbind, solv, and −TΔS are calculated in the gas phase. ΔEMM is the gas phase molecular mechanical energy changes which includes covalent, electrostatic, and van der Waals energies.
T99 6516-6720 Sentence denotes Based on previous studies, the entropy change during binding is small and neglected in these calculations.48−50 ΔGbind, solv is the solvation free energy which comprises the polar and nonpolar components.
T100 6721-6854 Sentence denotes The polar solvation is calculated using the MMPBSA method by setting a value of 80 and 2 for solvent and solute dielectric constants.
T101 6855-6976 Sentence denotes The nonpolar free energy is simply estimated from the solvent accessible surface area (SASA) of the solute from the eq 5.

LitCovid-PubTator

Id Subject Object Predicate Lexical cue tao:has_database_id
377 70-75 Gene denotes hACE2 Gene:59272
378 135-139 Gene denotes ACE2 Gene:59272
379 306-310 Gene denotes ACE2 Gene:59272
380 735-739 Gene denotes ACE2 Gene:59272
381 932-936 Gene denotes ACE2 Gene:59272
382 1093-1097 Gene denotes ACE2 Gene:59272
383 519-526 Gene denotes GROMACS Gene:4082
384 40-44 Species denotes nCOV Tax:2697049
385 107-115 Species denotes SARS-COV Tax:694009
386 129-134 Species denotes human Tax:9606
387 217-221 Species denotes nCOV Tax:2697049
388 264-272 Species denotes SARS-COV Tax:694009
389 422-426 Species denotes nCOV Tax:2697049
390 433-441 Species denotes SARS-COV Tax:694009
391 479-483 Species denotes nCOV Tax:2697049
392 1151-1155 Species denotes nCOV Tax:2697049
393 454-461 Chemical denotes alanine MESH:D000409
394 538-543 Chemical denotes water MESH:D014867
395 747-751 Chemical denotes PBSA MESH:C437084
396 1124-1127 Chemical denotes Cys MESH:D003545
397 1198-1207 Chemical denotes disulfide MESH:D004220
398 1215-1221 Chemical denotes Cys336
399 1222-1228 Chemical denotes Cys361
400 1230-1236 Chemical denotes Cys379
401 1237-1243 Chemical denotes Cys432
402 1245-1251 Chemical denotes Cys391
403 1252-1258 Chemical denotes Cys525
404 1264-1270 Chemical denotes Cys480
405 1271-1277 Chemical denotes Cys488
407 1450-1458 Chemical denotes hydrogen MESH:D006859
411 3198-3205 Gene denotes GROMACS Gene:4082
412 3031-3039 Species denotes SARS-COV Tax:694009
413 3044-3048 Species denotes nCOV Tax:2697049
420 3542-3550 Species denotes SARS-COV Tax:694009
421 3552-3556 Species denotes nCOV Tax:2697049
422 3920-3928 Species denotes SARS-COV Tax:694009
423 3930-3934 Species denotes nCOV Tax:2697049
424 4523-4532 Disease denotes visual MD MESH:D009436
425 4534-4537 Disease denotes VMD
427 4943-4950 Gene denotes GROMACS Gene:4082
434 5306-5314 Species denotes SARS-COV Tax:694009
435 5319-5323 Species denotes nCOV Tax:2697049
436 5143-5147 Chemical denotes DCCM
437 5434-5442 Chemical denotes Hydrogen MESH:D006859
438 5215-5232 Disease denotes backbone Cα atoms
439 5466-5469 Disease denotes VMD
443 5781-5785 Gene denotes ACE2 Gene:59272
444 5813-5821 Species denotes SARS-COV Tax:694009
445 5826-5830 Species denotes nCOV Tax:2697049