Molecular Dynamics Reveals Complex Compensatory Effects of Ionic Strength on the Severe Acute Respiratory Syndrome Coronavirus 2 Spike/Human Angiotensin-Converting Enzyme 2 Interaction
| Autor: | Chuck S. Farah, Cristiane R. Guzzo, Anacleto Silva de Souza, Jose D. Rivera, Henning Ulrich, Pingju Ge, Roberto Kopke Salinas, Vitor Medeiros Almeida, Robson Francisco de Souza, Sandro R. Marana |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Letter Protein Conformation 0206 medical engineering Ionic bonding 02 engineering and technology Molecular Dynamics Simulation Hydrophobic effect 03 medical and health sciences Protein structure Protein Domains Viral entry Humans General Materials Science Amino Acid Sequence Physical and Theoretical Chemistry Surface plasmon resonance Receptor Host cell surface Binding Sites SARS-CoV-2 Chemistry Osmolar Concentration MICROBIOLOGIA Hydrogen Bonding 030104 developmental biology Ionic strength Spike Glycoprotein Coronavirus Biophysics Angiotensin-Converting Enzyme 2 Hydrophobic and Hydrophilic Interactions 020602 bioinformatics Protein Binding |
| Zdroj: | The Journal of Physical Chemistry Letters Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
| ISSN: | 1948-7185 |
| DOI: | 10.1021/acs.jpclett.0c02602 |
| Popis: | The SARS-CoV-2 pandemic has already killed more than one million people worldwide. To gain entry, the virus uses its Spike protein to bind to host hACE-2 receptors on the host cell surface and mediate fusion between viral and cell membranes. As initial steps leading to virus entry involve significant changes in protein conformation as well as in the electrostatic environment in the vicinity of the Spike/hACE-2 complex, we explored the sensitivity of the interaction to changes in ionic strength through computational simulations and surface plasmon resonance. We identified two regions in the receptor-binding domain (RBD), E1 and E2, which interact differently with hACE-2. At high salt concentration, E2-mediated interactions are weakened but are compensated by strengthening E1-mediated hydrophobic interactions. These results provide a detailed molecular understanding of Spike RBD/hACE-2 complex formation and stability under a wide range of ionic strengths. |
| Databáze: | OpenAIRE |
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