ArticleBriefings in bioinformatics2021
A model for pH coupling of the SARS-CoV-2 spike protein open/closed equilibrium.
Article in Briefings in bioinformatics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 25 citations in OpenAlex.
- Simulations of pH and thermal effects on SARS-CoV-2 spike glycoprotein.Frontiers in molecular biosciences · 2025Article
- Mammalian cell display with automated oligo design and library assembly allows for rapid residue level conformational epitope mapping.Communications biology · 2024Article
- Changes in total charge on spike protein of SARS-CoV-2 in emerging lineages.Bioinformatics advances · 2024Article
- #COVIDisAirborne: AI-enabled multiscale computational microscopy of delta SARS-CoV-2 in a respiratory aerosol.The international journal of high performance computing applications · 2023Article
- Electrostatics in Computational Biophysics and Its Implications for Disease Effects.International journal of molecular sciences · 2022Review
- Potential Use of Tea Tree Oil as a Disinfectant Agent against Coronaviruses: A Combined Experimental and Simulation Study.Molecules (Basel, Switzerland) · 2022Article
- The Physical Basis for pH Sensitivity in Biomolecular Structure and Function, With Application to the Spike Protein of SARS-CoV-2.Frontiers in molecular biosciences · 2022Review
- A stepwise mutagenesis approach using histidine and acidic amino acid to engineer highly pH-dependent protein switches.3 Biotech · 2022Article
- Structural and functional insights into the spike protein mutations of emerging SARS-CoV-2 variants.Cellular and molecular life sciences : CMLS · 2021Review
- Article
- #COVIDisAirborne: AI-Enabled Multiscale Computational Microscopy of Delta SARS-CoV-2 in a Respiratory Aerosol.bioRxiv : the preprint server for biology · 2021Article
- Structural-Dynamics and Binding Analysis of RBD from SARS-CoV-2 Variants of Concern (VOCs) and GRP78 Receptor Revealed Basis for Higher Infectivity.Microorganisms · 2021Article
- Conformational flexibility and structural variability of SARS-CoV2 S protein.Structure (London, England : 1993) · 2021Article
- Predicted pH-dependent stability of SARS-CoV-2 spike protein trimer from interfacial acidic groups.Computational and structural biotechnology journal · 2021Article
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Authors and funding
1 author at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causative agent of the coronavirus disease 2019 (COVID-19) pandemic, is thought to release its RNA genome at either the cell surface or within endosomes, the balance being dependent on spike protein stability, and the complement of receptors, co-receptors and proteases. To investigate possible mediators of pH-dependence, pKa calculations have been made on a set of structures for spike protein ectodomain and fragments from SARS-CoV-2 and other coronaviruses. Dominating a heat map of the aggregated predictions, three histidine residues in S2 are consistently predicted as destabilizing in pre-fusion (all three) and post-fusion (two of the three) structures. Other predicted features include the more moderate energetics of surface salt-bridge interactions and sidechain-mainchain interactions. Two aspartic acid residues in partially buried salt-bridges (D290-R273 and R355-D398) have pKas that are calculated to be elevated and destabilizing in more open forms of the spike trimer. These aspartic acids are most stabilized in a tightly closed conformation that has been observed when linoleic acid is bound, and which also affects the interactions of D614. The D614G mutation is known to modulate the balance of closed to open trimer. It is suggested that D398 in particular contributes to a pH-dependence of the open/closed equilibrium, potentially coupled to the effects of linoleic acid binding and D614G mutation, and possibly also A570D mutation. These observations are discussed in the context of SARS-CoV-2 infection, mutagenesis studies, and other human coronaviruses.
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