Comparison of umbrella sampling and steered molecular dynamics methods for computing free energy profiles of aromatic substrates through phospholipid bilayers

2020 ◽  
Vol 153 (3) ◽  
pp. 034115
Author(s):  
Sang Young Noh ◽  
Rebecca Notman
Keyword(s):  
Molecular Dynamics ◽  
Free Energy ◽  
Steered Molecular Dynamics ◽  
Umbrella Sampling ◽  
Phospholipid Bilayers ◽  
Energy Profiles ◽  
Aromatic Substrates ◽  
Molecular Dynamics Methods ◽  
Free Energy Profiles

The molecular mechanism of ligand unbinding from the human telomeric G-quadruplex by steered molecular dynamics and umbrella sampling simulations

2015 ◽  
Vol 17 (19) ◽  
pp. 12857-12869 ◽  
Author(s):  
Jia-Kai Zhou ◽  
Dah-Yen Yang ◽  
Sheh-Yi Sheu
Keyword(s):  
Mechanical Properties ◽  
Molecular Dynamics ◽  
Free Energy ◽  
Molecular Mechanism ◽  
Steered Molecular Dynamics ◽  
Umbrella Sampling ◽  
Energy Profiles ◽  
G Quadruplex ◽  
Free Energy Profiles

The mechanical properties and kinetic pathways of the ligand BMVC unbinding from the G-quadruplex were investigated via the computation of free energy profiles.

scholarly journals Comparison of Umbrella Sampling and Steered Molecular Dynamics Methods for Computing Free Energy Profiles of Toluene Molecules through Phospholipid Bilayers

2019 ◽  
Author(s):  
Sang Noh ◽  
Rebecca Notman
Keyword(s):  
Molecular Dynamics ◽  
Free Energy ◽  
Computational Efficiency ◽  
Steered Molecular Dynamics ◽  
Umbrella Sampling ◽  
Energy Profiles ◽  
Toluene Molecule ◽  
Molecular Dynamics Methods ◽  
Viable Approach ◽  
The Cost

In this study, we use Molecular Dynamics (MD) to analyze three different corrections of the Steered Molecular Dynamics (SMD) implementation of Jarzynski's Equality (JE) to calculate the FE change for the translocation of a toluene molecule across a lipid bilayer, and compare the accuracy and computational efficiency of these approaches to the results obtained using Umbrella Sampling (US). We show that when computing the free energy profile of a small molecule across a model membrane, the SMD approach suffers from sampling issues that may be alleviated through the use of a slower pulling velocity, but at the cost of computational efficiency. We deduce that, despite its drawbacks, US remains the more viable approach of the two for computing the free energy (FE) profile.

scholarly journals Comparison of Umbrella Sampling and Steered Molecular Dynamics Methods for Computing Free Energy Profiles of Toluene Molecules through Phospholipid Bilayers

2019 ◽  
Author(s):  
Sang Noh ◽  
Rebecca Notman
Keyword(s):  
Molecular Dynamics ◽  
Free Energy ◽  
Computational Efficiency ◽  
Steered Molecular Dynamics ◽  
Umbrella Sampling ◽  
Energy Profiles ◽  
Toluene Molecule ◽  
Molecular Dynamics Methods ◽  
Viable Approach ◽  
The Cost

In this study, we use Molecular Dynamics (MD) to analyze three different corrections of the Steered Molecular Dynamics (SMD) implementation of Jarzynski's Equality (JE) to calculate the FE change for the translocation of a toluene molecule across a lipid bilayer, and compare the accuracy and computational efficiency of these approaches to the results obtained using Umbrella Sampling (US). We show that when computing the free energy profile of a small molecule across a model membrane, the SMD approach suffers from sampling issues that may be alleviated through the use of a slower pulling velocity, but at the cost of computational efficiency. We deduce that, despite its drawbacks, US remains the more viable approach of the two for computing the free energy (FE) profile.

Displacement of carbonates in Ca2UO2(CO3)3 by amidoxime-based ligands from free-energy simulations

2018 ◽  
Vol 47 (5) ◽  
pp. 1604-1613 ◽  
Author(s):  
Bo Li ◽  
Chad Priest ◽  
De-en Jiang
Keyword(s):  
Molecular Dynamics ◽  
Free Energy ◽  
Molecular Dynamics Simulations ◽  
Umbrella Sampling ◽  
Nacl Solution ◽  
Classical Molecular Dynamics ◽  
Energy Profiles ◽  
Energy Simulations ◽  
Dynamics Simulations ◽  
Free Energy Profiles

Classical molecular dynamics simulations coupled with umbrella sampling reveal the atomistic processes and free-energy profiles of the displacement of carbonate groups in the Ca2UO2(CO3)3 complex by amidoxime-based ligands in a 0.5 M NaCl solution.

Comparison of Umbrella Sampling and Steered Molecular Dynamics Methods for Computing Free Energy Profiles of Aromatic Substrates through Phospholipid Bilayers

2020 ◽  
Author(s):  
Sang Noh ◽  
Rebecca Notman
Keyword(s):  
Molecular Dynamics ◽  
Free Energy ◽  
Lipid Bilayer ◽  
Lipid Membranes ◽  
Steered Molecular Dynamics ◽  
Umbrella Sampling ◽  
Reaction Coordinate ◽  
Aromatic Substrates ◽  
Show Evidence ◽  
Viable Approach

Understanding the permeation of molecules through lipid membranes is fundamental for predicting the cellular uptake of solutes and drug delivery mechanisms. In molecular simulations the usual approach is to compute the free energy (FE) profile of a molecule across a model lipid bilayer, which can then be used to estimate the permeability of the molecule. Umbrella sampling (US), which involves carrying out a series of biased simulations along a defined reaction coordinate (usually the bilayer normal direction), is a popular method for the computation of such FE profiles. However, US can be challenging to implement because the results are dependent on the strength of the biasing potential and the spacing of windows along the reaction coordinate, which, in practice, are usually optimized by an inefficient trial and error approach. The Steered Molecular Dynamics implementation of the Jarzynski Equality (JE-SMD) has been identified as an alternative to equilibrium sampling methods for measuring the FE change across a reaction coordinate. In the JE-SMD approach, equilibrium FE values are evaluated from the average of rapid non-equilibrium trajectories, thus avoiding the practical issues that come with US. Here, we use three different corrections of the JE-SMD method to calculate the FE change for the translocation of two aromatic substrates, phenylalanine and toluene, across a lipid bilayer, and compare the accuracy and computational efficiency of these approaches to the results obtained using US. We show evidence that when computing the free energy profile, the JE-SMD approach suffers from insufficient sampling convergence of the bilayer environment, and is dependent on the characteristic of the aromatic substrate itself. We deduce that, despite its drawbacks, US remains the more viable approach of the two for computing the FE profile.

Comparison of Umbrella Sampling and Steered Molecular Dynamics Methods for Computing Free Energy Profiles of Aromatic Substrates through Phospholipid Bilayers

2020 ◽  
Author(s):  
Sang Noh ◽  
Rebecca Notman
Keyword(s):  
Molecular Dynamics ◽  
Free Energy ◽  
Lipid Bilayer ◽  
Lipid Membranes ◽  
Steered Molecular Dynamics ◽  
Umbrella Sampling ◽  
Reaction Coordinate ◽  
Aromatic Substrates ◽  
Show Evidence ◽  
Viable Approach

Understanding the permeation of molecules through lipid membranes is fundamental for predicting the cellular uptake of solutes and drug delivery mechanisms. In molecular simulations the usual approach is to compute the free energy (FE) profile of a molecule across a model lipid bilayer, which can then be used to estimate the permeability of the molecule. Umbrella sampling (US), which involves carrying out a series of biased simulations along a defined reaction coordinate (usually the bilayer normal direction), is a popular method for the computation of such FE profiles. However, US can be challenging to implement because the results are dependent on the strength of the biasing potential and the spacing of windows along the reaction coordinate, which, in practice, are usually optimized by an inefficient trial and error approach. The Steered Molecular Dynamics implementation of the Jarzynski Equality (JE-SMD) has been identified as an alternative to equilibrium sampling methods for measuring the FE change across a reaction coordinate. In the JE-SMD approach, equilibrium FE values are evaluated from the average of rapid non-equilibrium trajectories, thus avoiding the practical issues that come with US. Here, we use three different corrections of the JE-SMD method to calculate the FE change for the translocation of two aromatic substrates, phenylalanine and toluene, across a lipid bilayer, and compare the accuracy and computational efficiency of these approaches to the results obtained using US. We show evidence that when computing the free energy profile, the JE-SMD approach suffers from insufficient sampling convergence of the bilayer environment, and is dependent on the characteristic of the aromatic substrate itself. We deduce that, despite its drawbacks, US remains the more viable approach of the two for computing the FE profile.

On the use of the adiabatic molecular dynamics technique in the calculation of free energy profiles

2002 ◽  
Vol 116 (11) ◽  
pp. 4389-4402 ◽  
Author(s):  
Lula Rosso ◽  
Peter Mináry ◽  
Zhongwei Zhu ◽  
Mark E. Tuckerman
Keyword(s):  
Molecular Dynamics ◽  
Free Energy ◽  
Energy Profiles ◽  
Free Energy Profiles

Energetics of nonpolar and polar compounds in cationic, anionic, and nonionic micelles studied by all-atom molecular dynamics simulation combined with a theory of solutions

2016 ◽  
Vol 18 (19) ◽  
pp. 13223-13231 ◽  
Author(s):  
Atsushi Date ◽  
Ryosuke Ishizuka ◽  
Nobuyuki Matubayasi
Keyword(s):  
Molecular Dynamics ◽  
Free Energy ◽  
Molecular Dynamics Simulation ◽  
Polar Compounds ◽  
Dynamics Simulation ◽  
Energy Profiles ◽  
Polar Solutes ◽  
Free Energy Profiles

Free-energy profiles of binding nonpolar and polar solutes in cationic, anionic, and nonionic micelles.

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