scholarly journals Thermodynamics and Kinetics in Antibody Resistance of the 501Y.V2 SARS-CoV-2 Variant

2021 ◽  
Author(s):  
Son Tung Ngo ◽  
Trung Hai Nguyen ◽  
Duc-Hung Pham ◽  
Nguyen Thanh Tung ◽  
Pham Cam Nam
Keyword(s):  
Free Energy ◽  
South African ◽  
Binding Free Energy ◽  
Energy Landscape ◽  
Neutralizing Antibody ◽  
Receptor Binding Domain ◽  
The South ◽  
Thermodynamics And Kinetics ◽  
Antibody Resistance ◽  
Kinetics Of

Understanding thermodynamics and kinetics of the binding process of antibody to SARS-CoV-2 receptor-binding domain (RBD) of Spike protein is very important for the development of COVID19 vaccines. Especially, it is essential to understand how the binding mechanism may change under the effects of RBD mutations. In this context, we have demonstrated that the South African variant (B1.351 or 501Y.V2) can resist the neutralizing antibody (NAb). Three substitutions in RBD including K417N, E484K, and N501Y alters the free energy landscape, binding pose, binding free energy, binding kinetics, and unbinding pathway of RBD + NAb complexes. The low binding affinity of NAb to 501Y.V2 RBD confirms the antibody resistance of the South African variant.

scholarly journals Thermodynamics and Kinetics in Antibody Resistance of the 501Y.V2 SARS-CoV-2 Variant

2021 ◽  
Author(s):  
Son Tung Ngo ◽  
Trung Hai Nguyen ◽  
Duc-Hung Pham ◽  
Nguyen Thanh Tung ◽  
Pham Cam Nam
Keyword(s):  
Free Energy ◽  
South African ◽  
Binding Free Energy ◽  
Energy Landscape ◽  
Neutralizing Antibody ◽  
Receptor Binding Domain ◽  
The South ◽  
Thermodynamics And Kinetics ◽  
Antibody Resistance ◽  
Kinetics Of

Understanding thermodynamics and kinetics of the binding process of antibody to SARS-CoV-2 receptor-binding domain (RBD) of Spike protein is very important for the development of COVID19 vaccines. Especially, it is essential to understand how the binding mechanism may change under the effects of RBD mutations. In this context, we have demonstrated that the South African variant (B1.351 or 501Y.V2) can resist the neutralizing antibody (NAb). Three substitutions in RBD including K417N, E484K, and N501Y alters the free energy landscape, binding pose, binding free energy, binding kinetics, and unbinding pathway of RBD + NAb complexes. The low binding affinity of NAb to 501Y.V2 RBD confirms the antibody resistance of the South African variant.

scholarly journals Thermodynamics and Kinetics in Antibody Resistance of the 501Y.V2 SARS-CoV-2 Variant

2021 ◽  
Author(s):  
Son Tung Ngo ◽  
Trung Hai Nguyen ◽  
Duc-Hung Pham ◽  
Nguyen Thanh Tung ◽  
Pham Cam Nam
Keyword(s):  
Free Energy ◽  
South African ◽  
Binding Free Energy ◽  
Energy Landscape ◽  
Neutralizing Antibody ◽  
Receptor Binding Domain ◽  
The South ◽  
Thermodynamics And Kinetics ◽  
Antibody Resistance ◽  
Kinetics Of

Understanding thermodynamics and kinetics of the binding process of antibody to SARS-CoV-2 receptor-binding domain (RBD) of Spike protein is very important for the development of COVID19 vaccines. Especially, it is essential to understand how the binding mechanism may change under the effects of RBD mutations. In this context, we have demonstrated that the South African variant (B1.351 or 501Y.V2) can resist the neutralizing antibody (NAb). Three substitutions in RBD including K417N, E484K, and N501Y alters the free energy landscape, binding pose, binding free energy, binding kinetics, and unbinding pathway of RBD + NAb complexes. The low binding affinity of NAb to 501Y.V2 RBD confirms the antibody resistance of the South African variant.

scholarly journals Thermodynamics and Kinetics in Antibody Resistance of the 501Y.V2 SARS-CoV-2 Variant

2021 ◽  
Author(s):  
Son Tung Ngo ◽  
Trung Hai Nguyen ◽  
Duc-Hung Pham ◽  
Nguyen Thanh Tung ◽  
Pham Cam Nam
Keyword(s):  
Free Energy ◽  
South African ◽  
Binding Free Energy ◽  
Energy Landscape ◽  
Neutralizing Antibody ◽  
Receptor Binding Domain ◽  
The South ◽  
Thermodynamics And Kinetics ◽  
Antibody Resistance ◽  
Kinetics Of

Understanding thermodynamics and kinetics of the binding process of antibody to SARS-CoV-2 receptor-binding domain (RBD) of Spike protein is very important for the development of COVID19 vaccines. Especially, it is essential to understand how the binding mechanism may change under the effects of RBD mutations. In this context, we have demonstrated that the South African variant (B1.351 or 501Y.V2) can resist the neutralizing antibody (NAb). Three substitutions in RBD including K417N, E484K, and N501Y alters the free energy landscape, binding pose, binding free energy, binding kinetics, and unbinding pathway of RBD + NAb complexes. The low binding affinity of NAb to 501Y.V2 RBD confirms the antibody resistance of the South African variant.

scholarly journals Thermodynamics and Kinetics in Antibody Resistance of the 501Y.V2 SARS-CoV-2 Variant

2021 ◽  
Author(s):  
Son Tung Ngo ◽  
Trung Hai Nguyen ◽  
Duc-Hung Pham ◽  
Nguyen Thanh Tung ◽  
Pham Cam Nam
Keyword(s):  
Free Energy ◽  
South African ◽  
Binding Free Energy ◽  
Neutralizing Antibody ◽  
Receptor Binding Domain ◽  
The South ◽  
Binding Process ◽  
Thermodynamics And Kinetics ◽  
Antibody Resistance ◽  
Kinetics Of

<div> <p><a>Understanding thermodynamics and kinetics of the binding process of an antibody to SARS-CoV-2 receptor-binding domain (RBD) of Spike protein is very important for the development of COVID19 vaccines. Especially, it is essential to understand how the binding mechanism may change under the effects of RBD mutations. In this context, we have demonstrated that the South African variant (B1.351 or 501Y.V2) can resist the neutralizing antibody (NAb). Three substitutions in RBD including K417N, E484K, and N501Y alters the free energy landscape, binding pose, binding free energy, binding kinetics, hydrogen bond, nonbonded contacts, and unbinding pathway of RBD + NAb complexes. The low binding affinity of NAb to 501Y.V2 RBD confirms the antibody resistance of the South African variant.</a> Moreover, the fragment of NAb + RBD can be used as an affordable model to investigate the change of the binding process between mutations RBD and antibodies.</p></div>

scholarly journals Thermodynamics and kinetics of the F o F 1 -ATPase: application of the probability isotherm

2016 ◽  
Vol 3 (2) ◽  
pp. 150379 ◽  
Author(s):  
Brian Chapman ◽  
Denis Loiselle
Keyword(s):  
Free Energy ◽  
Numerical Solution ◽  
Atp Synthesis ◽  
Enzyme Activation ◽  
Thermodynamic Efficiency ◽  
Second Law ◽  
Metabolic Rates ◽  
Thermodynamics And Kinetics ◽  
Rotary Mechanism ◽  
Kinetics Of

We use the results of recent publications as vehicles with which to discuss the thermodynamics of the proton-driven mitochondrial F o F 1 -ATP synthase, focusing particularly on the possibility that there may be dissociation between rotatory steps and ATP synthesis/hydrolysis. Such stoichiometric ‘slippage’ has been invoked in the literature to explain observed non-ideal behaviour. Numerical solution of the Rate Isotherm (the kinetic equivalent of the more fundamental Probability Isotherm) suggests that such ‘slippage’ is an unlikely explanation; instead, we suggest that the experimental results may be more consistent with damage to the enzyme caused by its isolation from the biomembrane and its experimental fixation, resulting in non-physiological friction within the enzyme's rotary mechanism. We emphasize the unavoidable constraint of the Second Law as instantiated by the obligatory dissipation of Gibbs Free Energy if the synthase is to operate at anything other than thermodynamic equilibrium. We use further numerical solution of the Rate Isotherm to demonstrate that there is no necessary association of low thermodynamic efficiency with high metabolic rates in a bio-world in which the dominating mechanism of metabolic control is multifactorial enzyme activation.

scholarly journals Unraveling the SARS-CoV-2 Main Protease Mechanism Using Multiscale DFT/MM Methods

2020 ◽  
Author(s):  
Carlos A. Ramos-Guzmán ◽  
J. Javier Ruiz-Pernía ◽  
Iñaki Tuñón
Keyword(s):  
Active Site ◽  
Energy Landscape ◽  
Multiscale Simulation ◽  
Free Energy Landscape ◽  
Simulation Methods ◽  
Thermodynamics And Kinetics ◽  
Main Protease ◽  
Key Factor ◽  
Inhibition Process ◽  
Kinetics Of

<p>We present a detailed theoretical analysis of the reaction mechanism of proteolysis catalyzed by the main protease of SARS-CoV-2. Using multiscale simulation methods, we have characterized the interactions stablished by a peptidic substrate in the active site and then we have explored the free energy landscape associated to the acylation and de-acylation steps of the proteolysis reaction, characterizing the transition states of the process. Our mechanistic proposals can explain most of the experimental observations made on the highly similar ortholog protease of SARS-CoV. We point out to some key interactions that may facilitate the acylation process and thus can be crucial in the design of more specific and efficient inhibitors of the main protease activity. In particular, from our results, the P1’ residue can be a key factor to improve the thermodynamics and kinetics of the inhibition process.</p>

scholarly journals Reduced binding and neutralization of infection- and vaccine-induced antibodies to the B.1.351 (South African) SARS-CoV-2 variant

2021 ◽  
Author(s):  
Venkata Viswanadh Edara ◽  
Carson Norwood ◽  
Katharine Floyd ◽  
Lilin Lai ◽  
Meredith E. Davis-Gardner ◽  
...  
Keyword(s):  
South African ◽  
Receptor Binding ◽  
Symptom Onset ◽  
Protective Immunity ◽  
Neutralizing Antibody ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
Live Virus ◽  
Fold Reduction ◽  
Antibody Titers

SUMMARYThe emergence of SARS-CoV-2 variants with mutations in the spike protein is raising concerns about the efficacy of infection- or vaccine-induced antibodies to neutralize these variants. We compared antibody binding and live virus neutralization of sera from naturally infected and spike mRNA vaccinated individuals against a circulating SARS-CoV-2 B.1 variant and the emerging B.1.351 variant. In acutely-infected (5-19 days post-symptom onset), convalescent COVID-19 individuals (through 8 months post-symptom onset) and mRNA-1273 vaccinated individuals (day 14 post-second dose), we observed an average 4.3-fold reduction in antibody titers to the B.1.351-derived receptor binding domain of the spike protein and an average 3.5-fold reduction in neutralizing antibody titers to the SARS-CoV-2 B.1.351 variant as compared to the B.1 variant (spike D614G). However, most acute and convalescent sera from infected and all vaccinated individuals neutralize the SARS-CoV-2 B.1.351 variant, suggesting that protective immunity is retained against COVID-19.

scholarly journals Imaging G protein–coupled receptors while quantifying their ligand-binding free-energy landscape

2015 ◽  
Vol 12 (9) ◽  
pp. 845-851 ◽  
Author(s):  
David Alsteens ◽  
Moritz Pfreundschuh ◽  
Cheng Zhang ◽  
Patrizia M Spoerri ◽  
Shaun R Coughlin ◽  
...  
Keyword(s):  
Free Energy ◽  
Ligand Binding ◽  
G Protein ◽  
Binding Free Energy ◽  
Energy Landscape ◽  
G Protein Coupled Receptors ◽  
Free Energy Landscape ◽  
G Protein Coupled

scholarly journals The histone H3 N-terminal tail: a computational analysis of the free energy landscape and kinetics

2015 ◽  
Vol 17 (20) ◽  
pp. 13689-13698 ◽  
Author(s):  
Yuqing Zheng ◽  
Qiang Cui
Keyword(s):  
Free Energy ◽  
Energy Landscape ◽  
Critical Role ◽  
Histone H3 ◽  
Free Energy Landscape ◽  
Chromatin Dynamics ◽  
Markov State Models ◽  
State Models ◽  
Dynamics Simulations ◽  
Kinetics Of

Extensive molecular dynamics simulations and Markov State models are used to characterize the free energy landscape and kinetics of the histone H3 N-terminal tail, which plays a critical role in regulating chromatin dynamics and gene activity.

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