Molecular dynamics simulation reveals a surface salt bridge forming a kinetic trap in unfolding of truncated Staphylococcal nuclease

2003 ◽  
Vol 50 (3) ◽  
pp. 507-515 ◽  
Author(s):  
Andreea D. Gruia ◽  
Stefan Fischer ◽  
Jeremy C. Smith
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulation ◽  
Salt Bridge ◽  
Staphylococcal Nuclease ◽  
Dynamics Simulation ◽  
Kinetic Trap

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.

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.

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.

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