Protein Footprinting, Conformational Dynamics and Interface-Adjacent Neutralization ‘Hotspots’ in the SARS-CoV-2 Spike Protein Receptor Binding Domain / Human ACE2 Interaction

18 December 2020, Version 1
This content is a preprint and has not undergone peer review at the time of posting.


This study provides an HDX-MS based analysis of the interaction between the SARS-CoV-2 spike protein and the human Angiotensin Converting Enzyme 2.

- The data agree exactly with the X-ray co-crystal structure of this complex, but provide additional information based on shifts in dynamics that are observed just outside the interface.

- These dynamic changes occur specifically in regions that are the primary targets of neutralizing antibodies that target spike protein, suggesting that the neutralization mechanism may result from suppression of dynamic shifts in the spike Receptor Binding Domain (RBD) that are necessary for favorable binding thermodynamics in the spike / ACE2 interaction.


Spike protein
ACE2 (angiotensin converting enzyme-2)
hydrogen deuterium exchange mass sp...
Hydrogen deuterium exchange
protein interaction
conformational dynamics


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