Related Experiment Video
Updated: Oct 3, 2025
06:39
High-throughput Confocal Imaging of Quantum Dot-Conjugated SARS-CoV-2 Spike Trimers to Track Binding and Endocytosis in HEK293T Cells
Published on: April 21, 2022
3.2K
Site Density Functional Theory and Structural Bioinformatics Analysis of the SARS-CoV Spike Protein and hACE2 Complex
Nitesh Kumawat1, Andrejs Tucs2, Soumen Bera3
1School of Mathematics, Statistics and Computational Sciences, Central University of Rajasthan, Ajmer 305817, India.
Molecules (Basel, Switzerland)
|February 15, 2022
Summary
Water bridges significantly enhance SARS-CoV-2 spike protein binding to human ACE2 receptors, unlike SARS-CoV-1. This interaction stabilizes the complex, aiding viral entry and impacting infectivity.
Area of Science:
- Structural biology
- Computational biophysics
- Virology
Background:
- The SARS-CoV-2 spike (S) glycoprotein mediates viral entry into host cells by binding to the human angiotensin-converting enzyme 2 (hACE2) receptor.
- The receptor-binding domain (RBD) of the spike protein is crucial for this interaction.
- Understanding the molecular mechanisms of spike-hACE2 binding is vital for developing antiviral strategies.
Purpose of the Study:
- To investigate the binding and conformational properties of SARS-CoV-2 spike protein RBD and hACE2 complexes.
- To elucidate the role of water-mediated interactions in the binding affinity and stability of these complexes.
- To compare these interactions with those of the SARS-CoV-1/hACE2 complex.
Main Methods:
- Classical site density functional theory (SDFT) and structural bioinformatics.
- Three-dimensional reference interaction site model (3DRISM) analysis.
- Conformational dynamics simulations.
Main Results:
- Water-mediated interactions, forming additional water bridges, significantly increase binding affinity between SARS-CoV-2 spike protein and hACE2 compared to SARS-CoV-1.
- The SARS-CoV-2 RBD exhibits a larger size and conformational changes compared to SARS-CoV-1, with the 'up' conformation showing stronger intermolecular interactions and specific H-bonds.
- Interfacial water stabilizes the SARS-CoV-2/hACE2 complex, leading to structural rigidification of the spike protein and influencing RBD dynamics and infectivity.
Conclusions:
- Water-mediated interactions play a critical role in enhancing the stability and binding of the SARS-CoV-2 spike protein to hACE2.
- Structural differences and conformational dynamics of the SARS-CoV-2 RBD contribute to its increased infectivity.
- These findings provide insights into viral entry mechanisms and potential therapeutic targets.
Related Concept Videos
01:49Conserved Binding Sites
4.5K
Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
4.5K
01:24Protein Organization
7.8K
Proteins are polymers of amino acid residues. They are versatile and responsible for different cellular functions, including DNA replication, molecular transport, catalysis, and structural support. Proteins have a hierarchical structure comprising at least three levels of organization: primary, secondary, and tertiary structure. Some large proteins have a quaternary structure where individual protein subunits are linked together.
The primary structure of a protein is its amino acid sequence....
The primary structure of a protein is its amino acid sequence....
7.8K
01:56Structural Protein Function
2.9K
2.9K
00:49Ligand Binding and Linkage
5.0K
Allosteric proteins have more than one ligand binding site; the binding of a ligand to any of these sites influences the binding of ligands to the other sites. When a protein is allosteric, its binding sites are called coupled or linked. In the case of enzymes, the site that binds to the substrate is known as the active site and the other site is known as the regulatory site. When a ligand binds to the regulatory site, this leads to conformational changes in the protein that can influence...
5.0K
02:26Protein Networks
4.1K
An organism can have thousands of different proteins, and these proteins must cooperate to ensure the health of an organism. Proteins bind to other proteins and form complexes to carry out their functions. Many proteins interact with multiple other proteins creating a complex network of protein interactions.
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
4.1K
02:04Protein-protein Interfaces
13.9K
Many proteins form complexes to carry out their functions, making protein-protein interactions (PPIs) essential for an organism's survival. Most PPIs are stabilized by numerous weak noncovalent chemical forces. The physical shape of the interfaces determines the way two proteins interact. Many globular proteins have closely-matching shapes on their surfaces, which form a large number of weak bonds. Additionally, many PPIs occur between two helices or between a surface cleft and a...
13.9K