VERIFICATION OF THE GENERALIZED BORN MODEL AT SHORT DISTANCES

The generalized Born (GB) model, one of the implicit solvent models, is widely applied in molecular dynamics (MD) simulations as a simple description of the solvation effect. In the GB model, an empirical function called the Still's formula, with the algorithmic simplicity, is utilized to calculate the solvation energy due to the polarization, termed as ΔG pol . Applications of the GB model have exhibited reasonable accuracy and high computational efficiency. However, there is still room for improvements. Most of the attempts to improve the GB model focus on optimizing effective Born radii. Contrarily, limited researches have been performed to improve the feasibility of the Still's formula. In this paper, analytical methods was applied to investigate the validity of the Still's formula at short distance. Taking advantage of the toroidal coordinates and Mehler–Fock transform, the analytical solutions of the GB model at short distances was derived explicitly for the first time. Additionally, the solvation energy was numerically computed using proper algorithms based on the analytical solutions and compared with ΔG pol calculated in the GB model. With the analysis on the deficiencies of the Still's formula at short distances, potential methods to improve the validity of the GB model were discussed.

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Generalized Born Implicit Solvent Models for Biomolecules

Annual Review of Biophysics ◽

10.1146/annurev-biophys-052118-115325 ◽

2019 ◽

Vol 48 (1) ◽

pp. 275-296 ◽

Cited By ~ 21

Author(s):

Alexey V. Onufriev ◽

David A. Case

Keyword(s):

Md Simulations ◽

Implicit Solvent ◽

Molecular Mechanics Calculations ◽

Generalized Born ◽

Solvent Models ◽

Explicit Consideration ◽

Aqueous Solvation ◽

Solvent Molecules ◽

The Individual ◽

Implicit Solvent Models

It would often be useful in computer simulations to use an implicit description of solvation effects, instead of explicitly representing the individual solvent molecules. Continuum dielectric models often work well in describing the thermodynamic aspects of aqueous solvation and can be very efficient compared to the explicit treatment of the solvent. Here, we review a particular class of so-called fast implicit solvent models, generalized Born (GB) models, which are widely used for molecular dynamics (MD) simulations of proteins and nucleic acids. These approaches model hydration effects and provide solvent-dependent forces with efficiencies comparable to molecular-mechanics calculations on the solute alone; as such, they can be incorporated into MD or other conformational searching strategies in a straightforward manner. The foundations of the GB model are reviewed, followed by examples of newer, emerging models and examples of important applications. We discuss their strengths and weaknesses, both for fidelity to the underlying continuum model and for the ability to replace explicit consideration of solvent molecules in macromolecular simulations.

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Generalized Born implicit solvent models for small molecule hydration free energies

Physical Chemistry Chemical Physics ◽

10.1039/c6cp07347f ◽

2017 ◽

Vol 19 (2) ◽

pp. 1677-1685 ◽

Cited By ~ 2

Author(s):

Martin Brieg ◽

Julia Setzler ◽

Steffen Albert ◽

Wolfgang Wenzel

Keyword(s):

Free Energy ◽

Small Molecules ◽

Implicit Solvent ◽

Free Energies ◽

Hydration Free Energy ◽

Energy Estimation ◽

Generalized Born ◽

Solvent Models ◽

Molecular Force ◽

Implicit Solvent Models

Hydration free energy estimation of small molecules from all-atom simulations was widely investigated in recent years, as it provides an essential test of molecular force fields and our understanding of solvation effects.

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Saving Significant Amount of Time in MD Simulations by Using an Implicit Solvent Model and Elevated Temperatures

ISRN Computational Biology ◽

10.1155/2013/640125 ◽

2013 ◽

Vol 2013 ◽

pp. 1-5 ◽

Cited By ~ 3

Author(s):

Ifat Shub ◽

Ehud Schreiber ◽

Yossef Kliger

Keyword(s):

Elevated Temperatures ◽

Md Simulations ◽

Implicit Solvent ◽

Dynamic Simulations ◽

Implicit Solvent Model ◽

Solvent Models ◽

Solvent Model ◽

Wide Range ◽

Implicit Solvent Models ◽

Computer Power

Molecular dynamic simulations are used for investigating various aspects of biological processes. Such simulations often require intensive computer power; therefore several solutions were developed to minimize the computer power needed, including the usage of elevated temperatures. Yet, such simulations are still not commonly used by the wide scientific community of chemists and biochemists. For about two years now, the molecular simulations suite GROMACS enables conducting simulations using implicit solvent models to further decrease runtimes. In order to quantify the saving in computer power, and to confirm the validity of the models, we followed the simple dissolution process of a single NaCl molecule. The results reveal approximately 350-fold decrease in real-world runtime when using an implicit solvent model and an elevated temperature, compared to using explicit water molecules and simulating at room temperature. In addition, in a wide range of temperatures, the dissolution times of NaCl are distributed, as expected, exponentially, both in explicit and in implicit solvent models, hence confirming the validity of the simulation approach. Hopefully, our findings will encourage many scientists to take advantage of the recent progress in the molecular dynamics field for various applications.

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The Role of Displacing Confined Solvent in the Conformational Equilibrium of β-Cyclodextrin

10.26434/chemrxiv.8983715.v1 ◽

2019 ◽

Author(s):

Peng He ◽

Sheila Sarkar ◽

Emilio Gallicchio ◽

Tom Kurtzman ◽

Lauren Wickstrom

Keyword(s):

Conformational Equilibrium ◽

Implicit Solvent ◽

Theory Analysis ◽

State Behavior ◽

Generalized Born ◽

Solvent Models ◽

Explicit Solvent ◽

Dynamics Simulations ◽

Opening And Closing

<p>This study investigates the role of hydration and its relationship to the conformational equilibrium of the host molecule β-cyclodextrin. Molecular dynamics simulations indicate that the unbound β-cyclodextrin exhibits two state behavior in explicit solvent due to the opening and closing of its cavity. In implicit solvent, these transitions are not observed and there is one dominant conformation of β-cyclodextrin with an open cavity. Based on these observations, we investigate the hypothesis that the expulsion of thermodynamically unfavorable water molecules into the bulk plays an important role in controlling the accessibility of the closed macrostate at room temperature. We compare the results of the molecular mechanics analytical generalized Born plus non-polar solvation approach to those obtained through Grid Inhomogeneous Solvation Theory analysis with explicit solvation to elucidate the thermodynamic forces at play. The calculations help to illustrate the deficiencies of continuum solvent models and demonstrate the key role of the thermodynamics of enclosed hydration in driving the conformational equilibrium of molecules in solution. </p>

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