Transferable Ion Force Fields in Water from a Simultaneous Optimization of Ion Solvation and Ion–Ion Interaction

<div>To model halogen bond phenomena using classical force fields, an extra-point (EP) of charge is frequently introduced at a given distance from the halogen (X) to emulate the σ-hole. The resulting molecular dynamics (MD) trajectories can be used in subsequent molecular mechanics (MM) combined with Poisson–Boltzmann and surface area calculations (MM PBSA) to estimate protein–ligand binding free energies (∆G<sub>bind</sub>). While EP addition improves the MM/MD description of halogen-containing systems, its effect on the calculation of solvation free energies (∆G<sub>solv</sub>) using the PBSA approach is yet to be assessed. As the PBSA calculations depend, among other parameters, on the empirical assignment of radii (PB radii), a problematic issue arises since standard halogen radii are smaller than the typical X· · · EP distances (usually corresponding to R<sub>min</sub>), thus placing the EP within the solvent dielectric. Herein, we performed a comprehensive study on the performance of PBSA (using three different setups) in the calculation of ∆Gsolv values for 142 halogenated compounds (bearing Cl, Br, or I) for which the experimental values are known. By conducting an optimization (minimizing the error against experimental values), we provide a new optimized set of halogen PB radii, for each PBSA setup, that should be used when the EP is located at R min in the context of GAFF. A simultaneous optimization of PB radii and X· · · EP distances shows that a wide range of distance/radius pairs can be used without significant loss of accuracy, therefore laying the basis for expanding this halogen radii optimization strategy to other force fields and EP implementations. As ligand ∆G<sub>solv</sub> estimation is an important term in the determination of protein–ligand ∆G<sub>bind</sub> , this work is particularly relevant in the framework of structure-based virtual screening and related computer-aided drug design routines.</div>

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Tackling Halogenated Species with PBSA: Effect of Emulating the σ-Hole

10.26434/chemrxiv.7660550.v2 ◽

2019 ◽

Author(s):

Rafael Nunes ◽

Diogo Vila Viçosa ◽

Paulo J. Costa

Keyword(s):

Force Fields ◽

Halogen Bond ◽

Significant Loss ◽

Simultaneous Optimization ◽

Optimization Strategy ◽

Free Energies ◽

Wide Range ◽

Problematic Issue ◽

Experimental Values ◽

Extra Point

<div>To model halogen bond phenomena using classical force fields, an extra-point (EP) of charge is frequently introduced at a given distance from the halogen (X) to emulate the σ-hole. The resulting molecular dynamics (MD) trajectories can be used in subsequent molecular mechanics (MM) combined with Poisson–Boltzmann and surface area calculations (MM PBSA) to estimate protein–ligand binding free energies (∆G<sub>bind</sub>). While EP addition improves the MM/MD description of halogen-containing systems, its effect on the calculation of solvation free energies (∆G<sub>solv</sub>) using the PBSA approach is yet to be assessed. As the PBSA calculations depend, among other parameters, on the empirical assignment of radii (PB radii), a problematic issue arises since standard halogen radii are smaller than the typical X· · · EP distances (usually corresponding to R<sub>min</sub>), thus placing the EP within the solvent dielectric. Herein, we performed a comprehensive study on the performance of PBSA (using three different setups) in the calculation of ∆Gsolv values for 142 halogenated compounds (bearing Cl, Br, or I) for which the experimental values are known. By conducting an optimization (minimizing the error against experimental values), we provide a new optimized set of halogen PB radii, for each PBSA setup, that should be used when the EP is located at R min in the context of GAFF. A simultaneous optimization of PB radii and X· · · EP distances shows that a wide range of distance/radius pairs can be used without significant loss of accuracy, therefore laying the basis for expanding this halogen radii optimization strategy to other force fields and EP implementations. As ligand ∆G<sub>solv</sub> estimation is an important term in the determination of protein–ligand ∆G<sub>bind</sub> , this work is particularly relevant in the framework of structure-based virtual screening and related computer-aided drug design routines.</div>

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Tackling Halogenated Species with PBSA: Effect of Emulating the σ-Hole

10.26434/chemrxiv.7660550.v1 ◽

2019 ◽

Author(s):

Rafael Nunes ◽

Diogo Vila Viçosa ◽

Paulo J. Costa

Keyword(s):

Force Fields ◽

Halogen Bond ◽

Significant Loss ◽

Simultaneous Optimization ◽

Optimization Strategy ◽

Free Energies ◽

Wide Range ◽

Problematic Issue ◽

Experimental Values ◽

Extra Point

<div>To model halogen bond phenomena using classical force fields, an extra-point (EP) of charge is frequently introduced at a given distance from the halogen (X) to emulate the σ hole. The resulting molecular dynamics (MD) trajectories can be used in subsequent molecular mechanics (MM) combined with Poisson–Boltzmann and surface area calculations (MM-PBSA) to estimate protein–ligand binding free energies (∆Gbind ). While EP addition improves the MM/MD description of halogen-containing systems, its effect on the calculation of solvation free energies (∆G solv ) using the PBSA approach is yet to be assessed. As the PBSA calculations depend, among other parameters, on the empirical assignment of radii (PB radii), a problematic issue arises since standard halogen radii are smaller than the typical X· · · EP distances (usually corresponding to R min ), thus placing the EP within the solvent dielectric. Herein, we performed a comprehensive study on the performance of PBSA (using three different calculation setups) in the calculation of ∆G solv values for 142 halogenated compounds (bearing Cl, Br, or I) for which the experimental values are known. By conducting an optimization (minimizing the error against experimental values), we provide a new optimized set of halogen PB radii for each PBSA setup to be used when the EP is located at R min . A simultaneous optimization of PB radii and X· · · EP distances shows that a wide range of distance/radius pairs can be used without significant loss of accuracy, therefore laying the basis for expanding this halogen radii optimization strategy to other force fields and EP implementations. As ligand ∆G solv estimation is an important term in the determination of protein–ligand ∆G bind , this work is particularly relevant in the framework of structure-based virtual screening and related computer-aided drug design routines.</div>

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Use of the Magnetostatic Analogue In Electromagnetic Lens Engineering

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100068795 ◽

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.

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