scholarly journals N439K Variant in Spike Protein Alter the Infection Efficiency and Antigenicity of SARS-CoV-2 Based on Molecular Dynamics Simulation

2021 ◽  
Vol 9 ◽  
Author(s):  
Wenyang Zhou ◽  
Chang Xu ◽  
Pingping Wang ◽  
Meng Luo ◽  
Zhaochun Xu ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulation ◽  
Protein Interactions ◽  
Neutralizing Antibody ◽  
Salt Bridge ◽  
Dynamics Simulation ◽  
Protein Protein Interactions ◽  
Infection Efficiency ◽  
Structural Mechanism ◽  
Angiotensin Converting Enzyme 2

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing an outbreak of coronavirus disease 2019 (COVID-19), has been undergoing various mutations. The analysis of the structural and energetic effects of mutations on protein-protein interactions between the receptor binding domain (RBD) of SARS-CoV-2 and angiotensin converting enzyme 2 (ACE2) or neutralizing monoclonal antibodies will be beneficial for epidemic surveillance, diagnosis, and optimization of neutralizing agents. According to the molecular dynamics simulation, a key mutation N439K in the SARS-CoV-2 RBD region created a new salt bridge with Glu329 of hACE2, which resulted in greater electrostatic complementarity, and created a weak salt bridge with Asp442 of RBD. Furthermore, the N439K-mutated RBD bound hACE2 with a higher affinity than wild-type, which may lead to more infectious. In addition, the N439K-mutated RBD was markedly resistant to the SARS-CoV-2 neutralizing antibody REGN10987, which may lead to the failure of neutralization. The results show consistent with the previous experimental conclusion and clarify the structural mechanism under affinity changes. Our methods will offer guidance on the assessment of the infection efficiency and antigenicity effect of continuing mutations in SARS-CoV-2.

scholarly journals N439K variant in spike protein may alter the infection efficiency and antigenicity of SARS-CoV-2 based on molecular dynamics simulation

2020 ◽  
Author(s):  
Wenyang Zhou ◽  
Chang Xu ◽  
Pingping Wang ◽  
Meng Luo ◽  
Zhaochun Xu ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulation ◽  
Protein Interactions ◽  
Neutralizing Antibodies ◽  
Neutralizing Antibody ◽  
Salt Bridge ◽  
Dynamics Simulation ◽  
Wild Type ◽  
Protein Protein Interactions ◽  
Angiotensin Converting Enzyme 2

ABSTRACTSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing an outbreak of coronavirus disease 2019 (COVID-19), has been undergoing various mutations. The analysis of the structural and energetic effects of mutations on protein-protein interactions between the receptor binding domain (RBD) of SARS-CoV-2 and angiotensin converting enzyme 2 (ACE2) or neutralizing monoclonal antibodies will be beneficial for epidemic surveillance, diagnosis, and optimization of neutralizing agents. According to the molecular dynamics simulation, a key mutation N439K in the SARS-CoV-2 RBD region created a new salt bridge which resulted in greater electrostatic complementarity. Furthermore, the N439K-mutated RBD bound hACE2 with a higher affinity than wild-type, which may lead to more infectious. In addition, the N439K-mutated RBD was markedly resistant to the SARS-CoV-2 neutralizing antibody REGN10987, which may lead to the failure of neutralization. These findings would offer guidance on the development of neutralizing antibodies and the prevention of COVID-19.

Computational Approaches for Elucidating Protein-Protein Interactions in Cation Channel Signaling

2020 ◽  
Vol 21 (2) ◽  
pp. 179-192
Author(s):  
Baichun Hu ◽  
Xiaoming Zheng ◽  
Ying Wang ◽  
Jian Wang ◽  
Fengjiao Zhang
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulation ◽  
Homology Modeling ◽  
Protein Interactions ◽  
Protein Docking ◽  
Cation Channel ◽  
Dynamics Simulation ◽  
Protein Protein Interactions ◽  
Molecular Graphics ◽  
Computational Approaches

Background: The lipid bilayer of the plasma membrane is impermeable to ions, yet changes in the flux of ions across the cell membrane are critical regulatory events in cells. Because of their regulatory roles in a range of physiological processes, such as electrical signaling in muscles and neurons, to name a few, these proteins are one of the most important drug targets. Objective: This review mainly focused on the computational approaches for elucidating proteinprotein interactions in cation channel signaling. Discussion: Due to continuously advanced facilities and technologies in computer sciences, the physical contacts of macromolecules of channel structures have been virtually visualized. Indeed, techniques like protein-protein docking, homology modeling, and molecular dynamics simulation are valuable tools for predicting the protein complex and refining channels with unreleased structures. Undoubtedly, these approaches will greatly expand the cation channel signaling research, thereby speeding up structure-based drug design and discovery. Conclusion: We introduced a series of valuable computational tools for elucidating protein-protein interactions in cation channel signaling, including molecular graphics, protein-protein docking, homology modeling, and molecular dynamics simulation.

scholarly journals Atomistic simulation of carbohydrate-protein complex formation: Hevein-32 domain

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Charles Oluremi Solanke ◽  
Dalibor Trapl ◽  
Zoran Šućur ◽  
Václav Mareška ◽  
Igor Tvaroška ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulation ◽  
Protein Interactions ◽  
Atomistic Simulation ◽  
Binding Mode ◽  
Dynamics Simulation ◽  
Conformational Selection ◽  
Protein Complex Formation ◽  
Small Molecule Ligands ◽  
Carbohydrate Ligand

AbstractInteractions between proteins and their small molecule ligands are of great importance for the process of drug design. Here we report an unbiased molecular dynamics simulation of systems containing hevein domain (HEV32) with N-acetylglucosamine mono-, di- or trisaccharide. Carbohydrate molecules were placed outside the binding site. Three of six simulations (6 × 2 μs) led to binding of a carbohydrate ligand into the binding mode in agreement with the experimentally determined structure. Unbinding was observed in one simulation (monosaccharide). There were no remarkable intermediates of binding for mono and disaccharide. Trisaccharide binding was initiated by formation of carbohydrate-aromatic CH/π interactions. Our results indicate that binding of ligands followed the model of conformational selection because the conformation of the protein ready for ligand binding was observed before the binding. This study extends the concept of docking by dynamics on carbohydrate-protein interactions.

scholarly journals Molecular Dynamics Simulation of Barnase: Contribution of Noncovalent Intramolecular Interaction to Thermostability

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Zhiguo Chen ◽  
Yi Fu ◽  
Wenbo Xu ◽  
Ming Li
Keyword(s):  
Molecular Dynamics ◽  
Thermal Stability ◽  
Molecular Dynamics Simulation ◽  
Root Mean Square ◽  
Clinical Medicine ◽  
Intramolecular Interaction ◽  
Salt Bridge ◽  
Dynamics Simulation ◽  
Mean Square ◽  
Thermal Stability Of

Bacillus amyloliquefaciensribonuclease Barnase (RNase Ba) is a 12 kD (kilodalton) small extracellular ribonuclease. It has broad application prospects in agriculture, clinical medicine, pharmaceutical, and so forth. In this work, the thermal stability of Barnase has been studied using molecular dynamics simulation at different temperatures. The present study focuses on the contribution of noncovalent intramolecular interaction to protein stability and how they affect the thermal stability of the enzyme. Profiles of root mean square deviation and root mean square fluctuation identify thermostable and thermosensitive regions of Barnase. Analyses of trajectories in terms of secondary structure content, intramolecular hydrogen bonds and salt bridge interactions indicate distinct differences in different temperature simulations. In the simulations, Four three-member salt bridge networks (Asp8-Arg110-Asp12, Arg83-Asp75-Arg87, Lys66-Asp93-Arg69, and Asp54-Lys27-Glu73) have been identified as critical salt bridges for thermostability which are maintained stably at higher temperature enhancing stability of three hydrophobic cores. The study may help enlighten our knowledge of protein structural properties, noncovalent interactions which can stabilize secondary peptide structures or promote folding, and also help understand their actions better. Such an understanding is required for designing efficient enzymes with characteristics for particular applications at desired working temperatures.

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