scholarly journals Z-DNA as a Touchstone for Additive Empirical Force Fields and a Refinement of the Alpha/Gamma DNA Torsions for AMBER

2021 ◽  
Author(s):  
Marie Zgarbová ◽  
Jiří Šponer ◽  
Petr Jurečka
Keyword(s):  
Force Fields ◽  
Z Dna

scholarly journals Z-DNA as a Touchstone for Additive Empirical Force Fields and a Refinement of the Alpha/Gamma DNA torsions for AMBER

2021 ◽  
Author(s):  
Marie Zgarbova ◽  
Jiri Sponer ◽  
Petr Jurecka
Keyword(s):  
Force Fields ◽  
Difficult Case ◽  
Additive Effects ◽  
Correct Description ◽  
Dna Complexes ◽  
Dna Motifs ◽  
Z Dna ◽  
Living Organisms ◽  
The Stability ◽  
Amber Force Fields

Although current AMBER force fields are relatively accurate for canonical B-DNA, many non-canonical structures are still described incorrectly. As non-canonical motifs are attracting increasing attention due to the role they play in living organisms, further improvement is desirable. Here, we have chosen Z-DNA molecule, can be considered a touchstone of the universality of empirical force fields, since the non-canonical α and γ backbone conformations native to Z-DNA are also found in protein-DNA complexes, i-motif DNA and other non-canonical DNAs. We show that spurious α/γ conformations occurring in simulations with current AMBER force fields, OL15 and bsc1, are largely due to inaccurate α/γ parameterization. Moreover, stabilization of native Z-DNA substates involving γ = trans conformations appears to be in conflict with the correct description of the canonical B-DNA structure. Because the balance of the native and spurious conformations is influenced by non-additive effects, this is a difficult case for an additive dihedral energy scheme such as AMBER. We propose new α/γ parameters, denoted OL21, and show that they improve the stability of native α/γ Z-DNA substates while keeping the canonical DNA description virtually unchanged, and thus represent a reasonable compromise within the additive force field framework. Although further extensive testing is needed, the new modification appears to be a promising step towards a more reliable description of non-canonical DNA motifs and provides the best performance for Z-DNA molecules among current AMBER force fields.

Use of the Magnetostatic Analogue In Electromagnetic Lens Engineering

1970 ◽  
Vol 28 ◽  
pp. 360-361
Author(s):  
John W. Coleman
Keyword(s):  
Boundary Conditions ◽  
High Performance ◽  
Force Fields ◽  
Optical Design ◽  
Direct Conversion ◽  
Design Engineering ◽  
Design Data ◽  
Scalar Potentials ◽  
Geometric Elements ◽  
At Will

In the design engineering of high performance electromagnetic lenses, the direct conversion of electron optical design data into drawings for reliable hardware is oftentimes difficult, especially in terms of how to mount parts to each other, how to tolerance dimensions, and how to specify finishes. An answer to this is in the use of magnetostatic analytics, corresponding to boundary conditions for the optical design. With such models, the magnetostatic force on a test pole along the axis may be examined, and in this way one may obtain priority listings for holding dimensions, relieving stresses, etc..The development of magnetostatic models most easily proceeds from the derivation of scalar potentials of separate geometric elements. These potentials can then be conbined at will because of the superposition characteristic of conservative force fields.

Hydration Free Energies of Organic Molecules in the FreeSolv Database Calculated with Polarized Atom In Molecules Atomic Charges and the GAFF Force Field.

2018 ◽  
Author(s):  
Maximiliano Riquelme ◽  
Alejandro Lara ◽  
David L. Mobley ◽  
Toon Vestraelen ◽  
Adelio R Matamala ◽  
...  
Keyword(s):  
Force Field ◽  
Functional Groups ◽  
Electrostatic Interactions ◽  
Organic Molecules ◽  
Force Fields ◽  
Chemical Elements ◽  
Atomic Charges ◽  
Free Energies ◽  
Molecular Systems ◽  
Solvent Model

<div>Computer simulations of bio-molecular systems often use force fields, which are combinations of simple empirical atom-based functions to describe the molecular interactions. Even though polarizable force fields give a more detailed description of intermolecular interactions, nonpolarizable force fields, developed several decades ago, are often still preferred because of their reduced computation cost. Electrostatic interactions play a major role in bio-molecular systems and are therein described by atomic point charges.</div><div>In this work, we address the performance of different atomic charges to reproduce experimental hydration free energies in the FreeSolv database in combination with the GAFF force field. Atomic charges were calculated by two atoms-in-molecules approaches, Hirshfeld-I and Minimal Basis Iterative Stockholder (MBIS). To account for polarization effects, the charges were derived from the solute's electron density computed with an implicit solvent model and the energy required to polarize the solute was added to the free energy cycle. The calculated hydration free energies were analyzed with an error model, revealing systematic errors associated with specific functional groups or chemical elements. The best agreement with the experimental data is observed for the MBIS atomic charge method, including the solvent polarization, with a root mean square error of 2.0 kcal mol<sup>-1</sup> for the 613 organic molecules studied. The largest deviation was observed for phosphor-containing molecules and the molecules with amide, ester and amine functional groups.</div>

Molecular Dynamics Using Non-Variational Polarizable Force Fields: Theory, Periodic Boundary Conditions Implementation and Application to the Bond Capacity Model

2019 ◽  
Author(s):  
Pier Paolo Poier ◽  
Louis Lagardere ◽  
Jean-Philip Piquemal ◽  
Frank Jensen
Keyword(s):  
Boundary Conditions ◽  
Periodic Boundary ◽  
Force Fields ◽  
Periodic Boundary Conditions ◽  
Computational Effort ◽  
Polarizable Force Fields ◽  
Energy Models ◽  
Capacity Model ◽  
Energy Gradient ◽  
Polarization Models

<div> <div> <div> <p>We extend the framework for polarizable force fields to include the case where the electrostatic multipoles are not determined by a variational minimization of the electrostatic energy. Such models formally require that the polarization response is calculated for all possible geometrical perturbations in order to obtain the energy gradient required for performing molecular dynamics simulations. </p><div> <div> <div> <p>By making use of a Lagrange formalism, however, this computational demanding task can be re- placed by solving a single equation similar to that for determining the electrostatic variables themselves. Using the recently proposed bond capacity model that describes molecular polarization at the charge-only level, we show that the energy gradient for non-variational energy models with periodic boundary conditions can be calculated with a computational effort similar to that for variational polarization models. The possibility of separating the equation for calculating the electrostatic variables from the energy expression depending on these variables without a large computational penalty provides flexibility in the design of new force fields. </p><div><div><div> </div> </div> </div> <p> </p><div> <div> <div> <p>variables themselves. Using the recently proposed bond capacity model that describes molecular polarization at the charge-only level, we show that the energy gradient for non-variational energy models with periodic boundary conditions can be calculated with a computational effort similar to that for variational polarization models. The possibility of separating the equation for calculating the electrostatic variables from the energy expression depending on these variables without a large computational penalty provides flexibility in the design of new force fields. </p> </div> </div> </div> </div> </div> </div> </div> </div> </div>

QUBEKit: Automating the Derivation of Force Field Parameters from Quantum Mechanics

2019 ◽  
Author(s):  
Joshua Horton ◽  
Alice Allen ◽  
Leela Dodda ◽  
Daniel Cole
Keyword(s):  
Quantum Mechanics ◽  
Force Field ◽  
Organic Molecules ◽  
Force Fields ◽  
Liquid Density ◽  
Small Organic Molecules ◽  
Automated Generation ◽  
Energy Of Hydration ◽  
Novel Method ◽  
Force Field Parameters

<div><div><div><p>Modern molecular mechanics force fields are widely used for modelling the dynamics and interactions of small organic molecules using libraries of transferable force field parameters. For molecules outside the training set, parameters may be missing or inaccurate, and in these cases, it may be preferable to derive molecule-specific parameters. Here we present an intuitive parameter derivation toolkit, QUBEKit (QUantum mechanical BEspoke Kit), which enables the automated generation of system-specific small molecule force field parameters directly from quantum mechanics. QUBEKit is written in python and combines the latest QM parameter derivation methodologies with a novel method for deriving the positions and charges of off-center virtual sites. As a proof of concept, we have re-derived a complete set of parameters for 109 small organic molecules, and assessed the accuracy by comparing computed liquid properties with experiment. QUBEKit gives highly competitive results when compared to standard transferable force fields, with mean unsigned errors of 0.024 g/cm3, 0.79 kcal/mol and 1.17 kcal/mol for the liquid density, heat of vaporization and free energy of hydration respectively. This indicates that the derived parameters are suitable for molecular modelling applications, including computer-aided drug design.</p></div></div></div>

QUBEKit: Automating the Derivation of Force Field Parameters from Quantum Mechanics

2019 ◽  
Author(s):  
Joshua Horton ◽  
Alice Allen ◽  
Leela Dodda ◽  
Daniel Cole
Keyword(s):  
Quantum Mechanics ◽  
Force Field ◽  
Organic Molecules ◽  
Force Fields ◽  
Liquid Density ◽  
Small Organic Molecules ◽  
Automated Generation ◽  
Energy Of Hydration ◽  
Novel Method ◽  
Force Field Parameters

<div><div><div><p>Modern molecular mechanics force fields are widely used for modelling the dynamics and interactions of small organic molecules using libraries of transferable force field parameters. For molecules outside the training set, parameters may be missing or inaccurate, and in these cases, it may be preferable to derive molecule-specific parameters. Here we present an intuitive parameter derivation toolkit, QUBEKit (QUantum mechanical BEspoke Kit), which enables the automated generation of system-specific small molecule force field parameters directly from quantum mechanics. QUBEKit is written in python and combines the latest QM parameter derivation methodologies with a novel method for deriving the positions and charges of off-center virtual sites. As a proof of concept, we have re-derived a complete set of parameters for 109 small organic molecules, and assessed the accuracy by comparing computed liquid properties with experiment. QUBEKit gives highly competitive results when compared to standard transferable force fields, with mean unsigned errors of 0.024 g/cm3, 0.79 kcal/mol and 1.17 kcal/mol for the liquid density, heat of vaporization and free energy of hydration respectively. This indicates that the derived parameters are suitable for molecular modelling applications, including computer-aided drug design.</p></div></div></div>

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