Free energy landscape of a biomolecule in dihedral principal component space: Sampling convergence and correspondence between structures and minima

2007 ◽  
Vol 67 (3) ◽  
pp. 569-578 ◽  
Author(s):  
Gia G. Maisuradze ◽  
David M. Leitner
Keyword(s):  
Free Energy ◽  
Energy Landscape ◽  
Principal Component ◽  
Free Energy Landscape

Construction of the free energy landscape of biomolecules via dihedral angle principal component analysis

2008 ◽  
Vol 128 (24) ◽  
pp. 245102 ◽  
Author(s):  
Alexandros Altis ◽  
Moritz Otten ◽  
Phuong H. Nguyen ◽  
Rainer Hegger ◽  
Gerhard Stock
Keyword(s):  
Principal Component Analysis ◽  
Free Energy ◽  
Dihedral Angle ◽  
Energy Landscape ◽  
Principal Component ◽  
Component Analysis ◽  
Free Energy Landscape

scholarly journals Mutations of SARS-CoV-2 RBD May Alter Its Molecular Structure to Improve Its Infection Efficiency

Biomolecules ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 1273
Author(s):  
Ahmed L. Alaofi ◽  
Mudassar Shahid
Keyword(s):  
Free Energy ◽  
Angiotensin Converting Enzyme ◽  
Receptor Binding ◽  
Neutralizing Antibodies ◽  
Energy Landscape ◽  
Principal Component ◽  
Md Simulations ◽  
Free Energy Landscape ◽  
Binding Motif ◽  
Converting Enzyme

The receptor-binding domain (RBD) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mediates the viral–host interaction and is a target for most neutralizing antibodies. Nevertheless, SARS-CoV-2 RBD mutations pose a threat due to their role in host cell entry via the human angiotensin-converting enzyme 2 receptor that might strengthen SARS-CoV-2 infectivity, viral load, or resistance against neutralizing antibodies. To understand the molecular structural link between RBD mutations and infectivity, the top five mutant RBDs (i.e., N501Y, E484K L452R, S477N, and N439K) were selected based on their recorded case numbers. These mutants along with wild-type (WT) RBD were studied through all-atom molecular dynamics (MD) simulations of 100 ns. The principal component analysis and the free energy landscape were used too. Interestingly, N501Y, N439K, and E484K mutations were observed to increase the rigidity in some RBD regions while increasing the flexibility of the receptor-binding motif (RBM) region, suggesting a compensation of the entropy penalty. However, S477N and L452R RBDs were observed to increase the flexibility of the RBM region while maintaining similar flexibility in other RBD regions in comparison to WT RBD. Therefore, both mutations (especially S477N) might destabilize the RBD structure, as loose conformation compactness was observed. The destabilizing effect of S477N RBD was consistent with previous work on S477N mutation. Finally, the free energy landscape results showed that mutations changed WT RBD conformation while local minima were maintained for all mutant RBDs. In conclusion, RBD mutations definitely impact the WT RBD structure and conformation as well as increase the binding affinity to angiotensin-converting enzyme receptor.

Determination of Base Flipping Free Energy Landscapes from Nonequilibrium Stratification

2019 ◽  
Author(s):  
Xiaohui Wang ◽  
Zhaoxi Sun
Keyword(s):  
Free Energy ◽  
Energy Landscape ◽  
Sampling Technique ◽  
Umbrella Sampling ◽  
Energy Simulation ◽  
Nonlinear Dependence ◽  
Free Energy Landscape ◽  
Convergence Criterion ◽  
Base Flipping ◽  
Convergence Behavior

<p>Correct calculation of the variation of free energy upon base flipping is crucial in understanding the dynamics of DNA systems. The free energy landscape along the flipping pathway gives the thermodynamic stability and the flexibility of base-paired states. Although numerous free energy simulations are performed in the base flipping cases, no theoretically rigorous nonequilibrium techniques are devised and employed to investigate the thermodynamics of base flipping. In the current work, we report a general nonequilibrium stratification scheme for efficient calculation of the free energy landscape of base flipping in DNA duplex. We carefully monitor the convergence behavior of the equilibrium sampling based free energy simulation and the nonequilibrium stratification and determine the empirical length of time blocks required for converged sampling. Comparison between the performances of equilibrium umbrella sampling and nonequilibrium stratification is given. The results show that nonequilibrium free energy simulation is able to give similar accuracy and efficiency compared with the equilibrium enhanced sampling technique in the base flipping cases. We further test a convergence criterion we previously proposed and it comes out that the convergence behavior determined by this criterion agrees with those given by the time-invariant behavior of PMF and the nonlinear dependence of standard deviation on the sample size. </p>

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