PMC:7443692 / 32629-35543 JSON TXT

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LitCovid-sample-CHEBI

LitCovid-sample-PD-NCBITaxon

{"project":"LitCovid-sample-PD-NCBITaxon","denotations":[{"id":"T89","span":{"begin":50,"end":60},"obj":"Species"},{"id":"T90","span":{"begin":100,"end":105},"obj":"Species"},{"id":"T91","span":{"begin":550,"end":560},"obj":"Species"},{"id":"T92","span":{"begin":1826,"end":1831},"obj":"Species"},{"id":"T93","span":{"begin":1854,"end":1864},"obj":"Species"},{"id":"T94","span":{"begin":1980,"end":1985},"obj":"Species"},{"id":"T95","span":{"begin":2008,"end":2018},"obj":"Species"},{"id":"T96","span":{"begin":2534,"end":2539},"obj":"Species"}],"attributes":[{"id":"A91","pred":"ncbi_taxonomy_id","subj":"T91","obj":"NCBItxid:2697049"},{"id":"A93","pred":"ncbi_taxonomy_id","subj":"T93","obj":"NCBItxid:2697049"},{"id":"A94","pred":"ncbi_taxonomy_id","subj":"T94","obj":"NCBItxid:9606"},{"id":"A92","pred":"ncbi_taxonomy_id","subj":"T92","obj":"NCBItxid:9606"},{"id":"A95","pred":"ncbi_taxonomy_id","subj":"T95","obj":"NCBItxid:2697049"},{"id":"A90","pred":"ncbi_taxonomy_id","subj":"T90","obj":"NCBItxid:9606"},{"id":"A89","pred":"ncbi_taxonomy_id","subj":"T89","obj":"NCBItxid:2697049"},{"id":"A96","pred":"ncbi_taxonomy_id","subj":"T96","obj":"NCBItxid:9606"}],"namespaces":[{"prefix":"NCBItxid","uri":"http://purl.bioontology.org/ontology/NCBITAXON/"}],"text":"MD Simulation of the Glycosylated Trimer Spike of SARS-CoV-2 in Complex with Glycosylated, Soluble, Human Ace 2 Reveals Protein and Glycan Interactions\nMD simulations were performed to examine the co-complex (generated from a crystal structure of the ACE2-RBD co-complex, PDB: 6M0J; Lan et al., 2020) of glycosylated S with glycosylated ACE2 with the three different glycoforms models (Abundance, Oxford Class, and Processed; Table S1; Videos S5, S6, and S7). Information from these analyses is laid out along the primary structure (sequence) of the SARS-CoV-2 S protomer and ACE2 highlighting regions of glycan-protein interaction observed in the MD simulations (Table S14; Videos S5, S6, and S7). Interestingly, two glycans on ACE2 (at N090 and N322), which are highlighted in Figure 7 A and shown in a more close-up view in Figure 7B, are predicted to form interactions with the S protein (Table S15). The N322 glycan interaction with the S trimer is outside of the receptor-binding domain, and the interaction is observed across multiple simulations and throughout each simulation (Figures 7A and 7B; Video S5, S6, and S7). The ACE2 glycan at N090 is close enough to the S trimer surface to repeatedly form interactions; however, the glycan arms interact with multiple regions of the surface over the course of the simulations, reflecting the relatively high degree of glycan dynamics (Figures 7A and 7B; Video S3). Inter-molecule glycan-glycan interactions are also observed repeatedly between the glycan at N546 of ACE2 and those in the S protein at residues N0074 and N0165 (Figure 7D; Table S16). Finally, a full view of the ACE2-S complex with Oxford class glycoforms on ACE2 illustrates the extensive glycosylation at the interface of the complex (Figure 7C; Video S4).\nFigure 7 Interactions of Glycosylated Soluble Human ACE2 and Glycosylated SARS-CoV-2 S Trimer Immunogen Revealed By 3D-Structural Modeling and MD Simulations\n(A) MD simulation of glycosylated soluble human ACE2 and glycosylated SARS-CoV-2 S trimer immunogen interaction (see Videos S5, S6, and S7). ACE2 (top) is colored red with glycans in pink, whereas S is colored white with glycans in dark gray. Highlighted are ACE2 glycans that interact with S that are magnified to the right.\n(B) Magnification of ACE2-S interface highlighting ACE2 glycan interactions by using 3D-SNFG icons (Thieker et al., 2016) with S protein (pink) as well as ACE2-S glycan-glycan interactions.\n(C) Magnification of dynamics trajectory of glycans at the interface of soluble human ACE2 and S (see Videos S3 and S4).\nVideo S3. Interface of ACE2-S Complex, Related to Figure 7C\nVideo S4. The Glycosylated ACE2-S Complex, Related to Figure 7C\nVideo S5. Abundance Glycoforms on ACE2-S Complex, Related to Figure 7A\nVideo S6. Oxford Class Glycoforms on ACE2-S Complex, Related to Figure 7A\nVideo S7. Processed Glycoforms on ACE2-S Complex, Related to Figure 7A"}

LitCovid-sample-sentences

{"project":"LitCovid-sample-sentences","denotations":[{"id":"T198","span":{"begin":0,"end":151},"obj":"Sentence"},{"id":"T199","span":{"begin":152,"end":276},"obj":"Sentence"},{"id":"T200","span":{"begin":277,"end":459},"obj":"Sentence"},{"id":"T201","span":{"begin":460,"end":698},"obj":"Sentence"},{"id":"T202","span":{"begin":699,"end":904},"obj":"Sentence"},{"id":"T203","span":{"begin":905,"end":1127},"obj":"Sentence"},{"id":"T204","span":{"begin":1128,"end":1419},"obj":"Sentence"},{"id":"T205","span":{"begin":1420,"end":1604},"obj":"Sentence"},{"id":"T206","span":{"begin":1605,"end":1779},"obj":"Sentence"},{"id":"T207","span":{"begin":1780,"end":1937},"obj":"Sentence"},{"id":"T208","span":{"begin":1938,"end":2078},"obj":"Sentence"},{"id":"T209","span":{"begin":2079,"end":2180},"obj":"Sentence"},{"id":"T210","span":{"begin":2181,"end":2263},"obj":"Sentence"},{"id":"T211","span":{"begin":2264,"end":2453},"obj":"Sentence"},{"id":"T212","span":{"begin":2454,"end":2574},"obj":"Sentence"},{"id":"T213","span":{"begin":2575,"end":2584},"obj":"Sentence"},{"id":"T214","span":{"begin":2585,"end":2634},"obj":"Sentence"},{"id":"T215","span":{"begin":2635,"end":2644},"obj":"Sentence"},{"id":"T216","span":{"begin":2645,"end":2698},"obj":"Sentence"},{"id":"T217","span":{"begin":2699,"end":2708},"obj":"Sentence"},{"id":"T218","span":{"begin":2709,"end":2769},"obj":"Sentence"},{"id":"T219","span":{"begin":2770,"end":2779},"obj":"Sentence"},{"id":"T220","span":{"begin":2780,"end":2843},"obj":"Sentence"},{"id":"T221","span":{"begin":2844,"end":2853},"obj":"Sentence"},{"id":"T222","span":{"begin":2854,"end":2914},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"text":"MD Simulation of the Glycosylated Trimer Spike of SARS-CoV-2 in Complex with Glycosylated, Soluble, Human Ace 2 Reveals Protein and Glycan Interactions\nMD simulations were performed to examine the co-complex (generated from a crystal structure of the ACE2-RBD co-complex, PDB: 6M0J; Lan et al., 2020) of glycosylated S with glycosylated ACE2 with the three different glycoforms models (Abundance, Oxford Class, and Processed; Table S1; Videos S5, S6, and S7). Information from these analyses is laid out along the primary structure (sequence) of the SARS-CoV-2 S protomer and ACE2 highlighting regions of glycan-protein interaction observed in the MD simulations (Table S14; Videos S5, S6, and S7). Interestingly, two glycans on ACE2 (at N090 and N322), which are highlighted in Figure 7 A and shown in a more close-up view in Figure 7B, are predicted to form interactions with the S protein (Table S15). The N322 glycan interaction with the S trimer is outside of the receptor-binding domain, and the interaction is observed across multiple simulations and throughout each simulation (Figures 7A and 7B; Video S5, S6, and S7). The ACE2 glycan at N090 is close enough to the S trimer surface to repeatedly form interactions; however, the glycan arms interact with multiple regions of the surface over the course of the simulations, reflecting the relatively high degree of glycan dynamics (Figures 7A and 7B; Video S3). Inter-molecule glycan-glycan interactions are also observed repeatedly between the glycan at N546 of ACE2 and those in the S protein at residues N0074 and N0165 (Figure 7D; Table S16). Finally, a full view of the ACE2-S complex with Oxford class glycoforms on ACE2 illustrates the extensive glycosylation at the interface of the complex (Figure 7C; Video S4).\nFigure 7 Interactions of Glycosylated Soluble Human ACE2 and Glycosylated SARS-CoV-2 S Trimer Immunogen Revealed By 3D-Structural Modeling and MD Simulations\n(A) MD simulation of glycosylated soluble human ACE2 and glycosylated SARS-CoV-2 S trimer immunogen interaction (see Videos S5, S6, and S7). ACE2 (top) is colored red with glycans in pink, whereas S is colored white with glycans in dark gray. Highlighted are ACE2 glycans that interact with S that are magnified to the right.\n(B) Magnification of ACE2-S interface highlighting ACE2 glycan interactions by using 3D-SNFG icons (Thieker et al., 2016) with S protein (pink) as well as ACE2-S glycan-glycan interactions.\n(C) Magnification of dynamics trajectory of glycans at the interface of soluble human ACE2 and S (see Videos S3 and S4).\nVideo S3. Interface of ACE2-S Complex, Related to Figure 7C\nVideo S4. The Glycosylated ACE2-S Complex, Related to Figure 7C\nVideo S5. Abundance Glycoforms on ACE2-S Complex, Related to Figure 7A\nVideo S6. Oxford Class Glycoforms on ACE2-S Complex, Related to Figure 7A\nVideo S7. Processed Glycoforms on ACE2-S Complex, Related to Figure 7A"}

LitCovid-sample-PD-MONDO

{"project":"LitCovid-sample-PD-MONDO","denotations":[{"id":"T60","span":{"begin":50,"end":60},"obj":"Disease"},{"id":"T61","span":{"begin":550,"end":560},"obj":"Disease"},{"id":"T62","span":{"begin":1854,"end":1864},"obj":"Disease"},{"id":"T63","span":{"begin":2008,"end":2018},"obj":"Disease"}],"attributes":[{"id":"A60","pred":"mondo_id","subj":"T60","obj":"http://purl.obolibrary.org/obo/MONDO_0100096"},{"id":"A61","pred":"mondo_id","subj":"T61","obj":"http://purl.obolibrary.org/obo/MONDO_0100096"},{"id":"A62","pred":"mondo_id","subj":"T62","obj":"http://purl.obolibrary.org/obo/MONDO_0100096"},{"id":"A63","pred":"mondo_id","subj":"T63","obj":"http://purl.obolibrary.org/obo/MONDO_0100096"}],"text":"MD Simulation of the Glycosylated Trimer Spike of SARS-CoV-2 in Complex with Glycosylated, Soluble, Human Ace 2 Reveals Protein and Glycan Interactions\nMD simulations were performed to examine the co-complex (generated from a crystal structure of the ACE2-RBD co-complex, PDB: 6M0J; Lan et al., 2020) of glycosylated S with glycosylated ACE2 with the three different glycoforms models (Abundance, Oxford Class, and Processed; Table S1; Videos S5, S6, and S7). Information from these analyses is laid out along the primary structure (sequence) of the SARS-CoV-2 S protomer and ACE2 highlighting regions of glycan-protein interaction observed in the MD simulations (Table S14; Videos S5, S6, and S7). Interestingly, two glycans on ACE2 (at N090 and N322), which are highlighted in Figure 7 A and shown in a more close-up view in Figure 7B, are predicted to form interactions with the S protein (Table S15). The N322 glycan interaction with the S trimer is outside of the receptor-binding domain, and the interaction is observed across multiple simulations and throughout each simulation (Figures 7A and 7B; Video S5, S6, and S7). The ACE2 glycan at N090 is close enough to the S trimer surface to repeatedly form interactions; however, the glycan arms interact with multiple regions of the surface over the course of the simulations, reflecting the relatively high degree of glycan dynamics (Figures 7A and 7B; Video S3). Inter-molecule glycan-glycan interactions are also observed repeatedly between the glycan at N546 of ACE2 and those in the S protein at residues N0074 and N0165 (Figure 7D; Table S16). Finally, a full view of the ACE2-S complex with Oxford class glycoforms on ACE2 illustrates the extensive glycosylation at the interface of the complex (Figure 7C; Video S4).\nFigure 7 Interactions of Glycosylated Soluble Human ACE2 and Glycosylated SARS-CoV-2 S Trimer Immunogen Revealed By 3D-Structural Modeling and MD Simulations\n(A) MD simulation of glycosylated soluble human ACE2 and glycosylated SARS-CoV-2 S trimer immunogen interaction (see Videos S5, S6, and S7). ACE2 (top) is colored red with glycans in pink, whereas S is colored white with glycans in dark gray. Highlighted are ACE2 glycans that interact with S that are magnified to the right.\n(B) Magnification of ACE2-S interface highlighting ACE2 glycan interactions by using 3D-SNFG icons (Thieker et al., 2016) with S protein (pink) as well as ACE2-S glycan-glycan interactions.\n(C) Magnification of dynamics trajectory of glycans at the interface of soluble human ACE2 and S (see Videos S3 and S4).\nVideo S3. Interface of ACE2-S Complex, Related to Figure 7C\nVideo S4. The Glycosylated ACE2-S Complex, Related to Figure 7C\nVideo S5. Abundance Glycoforms on ACE2-S Complex, Related to Figure 7A\nVideo S6. Oxford Class Glycoforms on ACE2-S Complex, Related to Figure 7A\nVideo S7. Processed Glycoforms on ACE2-S Complex, Related to Figure 7A"}

LitCovid-sample-UniProt

LitCovid-sample-PD-FMA

{"project":"LitCovid-sample-PD-FMA","denotations":[{"id":"T99","span":{"begin":120,"end":127},"obj":"Body_part"},{"id":"T100","span":{"begin":612,"end":619},"obj":"Body_part"},{"id":"T101","span":{"begin":884,"end":891},"obj":"Body_part"},{"id":"T102","span":{"begin":1545,"end":1552},"obj":"Body_part"},{"id":"T103","span":{"begin":2393,"end":2400},"obj":"Body_part"}],"attributes":[{"id":"A99","pred":"fma_id","subj":"T99","obj":"http://purl.org/sig/ont/fma/fma67257"},{"id":"A100","pred":"fma_id","subj":"T100","obj":"http://purl.org/sig/ont/fma/fma67257"},{"id":"A101","pred":"fma_id","subj":"T101","obj":"http://purl.org/sig/ont/fma/fma67257"},{"id":"A102","pred":"fma_id","subj":"T102","obj":"http://purl.org/sig/ont/fma/fma67257"},{"id":"A103","pred":"fma_id","subj":"T103","obj":"http://purl.org/sig/ont/fma/fma67257"}],"text":"MD Simulation of the Glycosylated Trimer Spike of SARS-CoV-2 in Complex with Glycosylated, Soluble, Human Ace 2 Reveals Protein and Glycan Interactions\nMD simulations were performed to examine the co-complex (generated from a crystal structure of the ACE2-RBD co-complex, PDB: 6M0J; Lan et al., 2020) of glycosylated S with glycosylated ACE2 with the three different glycoforms models (Abundance, Oxford Class, and Processed; Table S1; Videos S5, S6, and S7). Information from these analyses is laid out along the primary structure (sequence) of the SARS-CoV-2 S protomer and ACE2 highlighting regions of glycan-protein interaction observed in the MD simulations (Table S14; Videos S5, S6, and S7). Interestingly, two glycans on ACE2 (at N090 and N322), which are highlighted in Figure 7 A and shown in a more close-up view in Figure 7B, are predicted to form interactions with the S protein (Table S15). The N322 glycan interaction with the S trimer is outside of the receptor-binding domain, and the interaction is observed across multiple simulations and throughout each simulation (Figures 7A and 7B; Video S5, S6, and S7). The ACE2 glycan at N090 is close enough to the S trimer surface to repeatedly form interactions; however, the glycan arms interact with multiple regions of the surface over the course of the simulations, reflecting the relatively high degree of glycan dynamics (Figures 7A and 7B; Video S3). Inter-molecule glycan-glycan interactions are also observed repeatedly between the glycan at N546 of ACE2 and those in the S protein at residues N0074 and N0165 (Figure 7D; Table S16). Finally, a full view of the ACE2-S complex with Oxford class glycoforms on ACE2 illustrates the extensive glycosylation at the interface of the complex (Figure 7C; Video S4).\nFigure 7 Interactions of Glycosylated Soluble Human ACE2 and Glycosylated SARS-CoV-2 S Trimer Immunogen Revealed By 3D-Structural Modeling and MD Simulations\n(A) MD simulation of glycosylated soluble human ACE2 and glycosylated SARS-CoV-2 S trimer immunogen interaction (see Videos S5, S6, and S7). ACE2 (top) is colored red with glycans in pink, whereas S is colored white with glycans in dark gray. Highlighted are ACE2 glycans that interact with S that are magnified to the right.\n(B) Magnification of ACE2-S interface highlighting ACE2 glycan interactions by using 3D-SNFG icons (Thieker et al., 2016) with S protein (pink) as well as ACE2-S glycan-glycan interactions.\n(C) Magnification of dynamics trajectory of glycans at the interface of soluble human ACE2 and S (see Videos S3 and S4).\nVideo S3. Interface of ACE2-S Complex, Related to Figure 7C\nVideo S4. The Glycosylated ACE2-S Complex, Related to Figure 7C\nVideo S5. Abundance Glycoforms on ACE2-S Complex, Related to Figure 7A\nVideo S6. Oxford Class Glycoforms on ACE2-S Complex, Related to Figure 7A\nVideo S7. Processed Glycoforms on ACE2-S Complex, Related to Figure 7A"}

LitCovid-sample-PD-GO-BP-0

{"project":"LitCovid-sample-PD-GO-BP-0","denotations":[{"id":"T76","span":{"begin":1711,"end":1724},"obj":"http://purl.obolibrary.org/obo/GO_0070085"}],"text":"MD Simulation of the Glycosylated Trimer Spike of SARS-CoV-2 in Complex with Glycosylated, Soluble, Human Ace 2 Reveals Protein and Glycan Interactions\nMD simulations were performed to examine the co-complex (generated from a crystal structure of the ACE2-RBD co-complex, PDB: 6M0J; Lan et al., 2020) of glycosylated S with glycosylated ACE2 with the three different glycoforms models (Abundance, Oxford Class, and Processed; Table S1; Videos S5, S6, and S7). Information from these analyses is laid out along the primary structure (sequence) of the SARS-CoV-2 S protomer and ACE2 highlighting regions of glycan-protein interaction observed in the MD simulations (Table S14; Videos S5, S6, and S7). Interestingly, two glycans on ACE2 (at N090 and N322), which are highlighted in Figure 7 A and shown in a more close-up view in Figure 7B, are predicted to form interactions with the S protein (Table S15). The N322 glycan interaction with the S trimer is outside of the receptor-binding domain, and the interaction is observed across multiple simulations and throughout each simulation (Figures 7A and 7B; Video S5, S6, and S7). The ACE2 glycan at N090 is close enough to the S trimer surface to repeatedly form interactions; however, the glycan arms interact with multiple regions of the surface over the course of the simulations, reflecting the relatively high degree of glycan dynamics (Figures 7A and 7B; Video S3). Inter-molecule glycan-glycan interactions are also observed repeatedly between the glycan at N546 of ACE2 and those in the S protein at residues N0074 and N0165 (Figure 7D; Table S16). Finally, a full view of the ACE2-S complex with Oxford class glycoforms on ACE2 illustrates the extensive glycosylation at the interface of the complex (Figure 7C; Video S4).\nFigure 7 Interactions of Glycosylated Soluble Human ACE2 and Glycosylated SARS-CoV-2 S Trimer Immunogen Revealed By 3D-Structural Modeling and MD Simulations\n(A) MD simulation of glycosylated soluble human ACE2 and glycosylated SARS-CoV-2 S trimer immunogen interaction (see Videos S5, S6, and S7). ACE2 (top) is colored red with glycans in pink, whereas S is colored white with glycans in dark gray. Highlighted are ACE2 glycans that interact with S that are magnified to the right.\n(B) Magnification of ACE2-S interface highlighting ACE2 glycan interactions by using 3D-SNFG icons (Thieker et al., 2016) with S protein (pink) as well as ACE2-S glycan-glycan interactions.\n(C) Magnification of dynamics trajectory of glycans at the interface of soluble human ACE2 and S (see Videos S3 and S4).\nVideo S3. Interface of ACE2-S Complex, Related to Figure 7C\nVideo S4. The Glycosylated ACE2-S Complex, Related to Figure 7C\nVideo S5. Abundance Glycoforms on ACE2-S Complex, Related to Figure 7A\nVideo S6. Oxford Class Glycoforms on ACE2-S Complex, Related to Figure 7A\nVideo S7. Processed Glycoforms on ACE2-S Complex, Related to Figure 7A"}

LitCovid-sample-GO-BP

{"project":"LitCovid-sample-GO-BP","denotations":[{"id":"T72","span":{"begin":1711,"end":1724},"obj":"http://purl.obolibrary.org/obo/GO_0070085"}],"text":"MD Simulation of the Glycosylated Trimer Spike of SARS-CoV-2 in Complex with Glycosylated, Soluble, Human Ace 2 Reveals Protein and Glycan Interactions\nMD simulations were performed to examine the co-complex (generated from a crystal structure of the ACE2-RBD co-complex, PDB: 6M0J; Lan et al., 2020) of glycosylated S with glycosylated ACE2 with the three different glycoforms models (Abundance, Oxford Class, and Processed; Table S1; Videos S5, S6, and S7). Information from these analyses is laid out along the primary structure (sequence) of the SARS-CoV-2 S protomer and ACE2 highlighting regions of glycan-protein interaction observed in the MD simulations (Table S14; Videos S5, S6, and S7). Interestingly, two glycans on ACE2 (at N090 and N322), which are highlighted in Figure 7 A and shown in a more close-up view in Figure 7B, are predicted to form interactions with the S protein (Table S15). The N322 glycan interaction with the S trimer is outside of the receptor-binding domain, and the interaction is observed across multiple simulations and throughout each simulation (Figures 7A and 7B; Video S5, S6, and S7). The ACE2 glycan at N090 is close enough to the S trimer surface to repeatedly form interactions; however, the glycan arms interact with multiple regions of the surface over the course of the simulations, reflecting the relatively high degree of glycan dynamics (Figures 7A and 7B; Video S3). Inter-molecule glycan-glycan interactions are also observed repeatedly between the glycan at N546 of ACE2 and those in the S protein at residues N0074 and N0165 (Figure 7D; Table S16). Finally, a full view of the ACE2-S complex with Oxford class glycoforms on ACE2 illustrates the extensive glycosylation at the interface of the complex (Figure 7C; Video S4).\nFigure 7 Interactions of Glycosylated Soluble Human ACE2 and Glycosylated SARS-CoV-2 S Trimer Immunogen Revealed By 3D-Structural Modeling and MD Simulations\n(A) MD simulation of glycosylated soluble human ACE2 and glycosylated SARS-CoV-2 S trimer immunogen interaction (see Videos S5, S6, and S7). ACE2 (top) is colored red with glycans in pink, whereas S is colored white with glycans in dark gray. Highlighted are ACE2 glycans that interact with S that are magnified to the right.\n(B) Magnification of ACE2-S interface highlighting ACE2 glycan interactions by using 3D-SNFG icons (Thieker et al., 2016) with S protein (pink) as well as ACE2-S glycan-glycan interactions.\n(C) Magnification of dynamics trajectory of glycans at the interface of soluble human ACE2 and S (see Videos S3 and S4).\nVideo S3. Interface of ACE2-S Complex, Related to Figure 7C\nVideo S4. The Glycosylated ACE2-S Complex, Related to Figure 7C\nVideo S5. Abundance Glycoforms on ACE2-S Complex, Related to Figure 7A\nVideo S6. Oxford Class Glycoforms on ACE2-S Complex, Related to Figure 7A\nVideo S7. Processed Glycoforms on ACE2-S Complex, Related to Figure 7A"}

2_test

{"project":"2_test","denotations":[{"id":"32841605-32225176-19659521","span":{"begin":295,"end":299},"obj":"32225176"},{"id":"32841605-27514939-19659522","span":{"begin":2380,"end":2384},"obj":"27514939"}],"text":"MD Simulation of the Glycosylated Trimer Spike of SARS-CoV-2 in Complex with Glycosylated, Soluble, Human Ace 2 Reveals Protein and Glycan Interactions\nMD simulations were performed to examine the co-complex (generated from a crystal structure of the ACE2-RBD co-complex, PDB: 6M0J; Lan et al., 2020) of glycosylated S with glycosylated ACE2 with the three different glycoforms models (Abundance, Oxford Class, and Processed; Table S1; Videos S5, S6, and S7). Information from these analyses is laid out along the primary structure (sequence) of the SARS-CoV-2 S protomer and ACE2 highlighting regions of glycan-protein interaction observed in the MD simulations (Table S14; Videos S5, S6, and S7). Interestingly, two glycans on ACE2 (at N090 and N322), which are highlighted in Figure 7 A and shown in a more close-up view in Figure 7B, are predicted to form interactions with the S protein (Table S15). The N322 glycan interaction with the S trimer is outside of the receptor-binding domain, and the interaction is observed across multiple simulations and throughout each simulation (Figures 7A and 7B; Video S5, S6, and S7). The ACE2 glycan at N090 is close enough to the S trimer surface to repeatedly form interactions; however, the glycan arms interact with multiple regions of the surface over the course of the simulations, reflecting the relatively high degree of glycan dynamics (Figures 7A and 7B; Video S3). Inter-molecule glycan-glycan interactions are also observed repeatedly between the glycan at N546 of ACE2 and those in the S protein at residues N0074 and N0165 (Figure 7D; Table S16). Finally, a full view of the ACE2-S complex with Oxford class glycoforms on ACE2 illustrates the extensive glycosylation at the interface of the complex (Figure 7C; Video S4).\nFigure 7 Interactions of Glycosylated Soluble Human ACE2 and Glycosylated SARS-CoV-2 S Trimer Immunogen Revealed By 3D-Structural Modeling and MD Simulations\n(A) MD simulation of glycosylated soluble human ACE2 and glycosylated SARS-CoV-2 S trimer immunogen interaction (see Videos S5, S6, and S7). ACE2 (top) is colored red with glycans in pink, whereas S is colored white with glycans in dark gray. Highlighted are ACE2 glycans that interact with S that are magnified to the right.\n(B) Magnification of ACE2-S interface highlighting ACE2 glycan interactions by using 3D-SNFG icons (Thieker et al., 2016) with S protein (pink) as well as ACE2-S glycan-glycan interactions.\n(C) Magnification of dynamics trajectory of glycans at the interface of soluble human ACE2 and S (see Videos S3 and S4).\nVideo S3. Interface of ACE2-S Complex, Related to Figure 7C\nVideo S4. The Glycosylated ACE2-S Complex, Related to Figure 7C\nVideo S5. Abundance Glycoforms on ACE2-S Complex, Related to Figure 7A\nVideo S6. Oxford Class Glycoforms on ACE2-S Complex, Related to Figure 7A\nVideo S7. Processed Glycoforms on ACE2-S Complex, Related to Figure 7A"}

PMC:7443692 / 32629-35543 JSONTXT

Annnotations TAB JSON ListView MergeView

PMC:7443692 / 32629-35543 JSON TXT