A Three-Dimensional Numerical Model of an Active Cell Cortex in the Viscous Limit

The cell cortex is a highly dynamic network of cytoskeletal filaments in which motor proteins induce active cortical stresses which in turn drive dynamic cellular processes such as cell motility, furrow formation or cytokinesis during cell division. Here, we develop a three-dimensional computational model of a cell cortex in the viscous limit including active cortical flows. Combining active gel and thin shell theory, we base our computational tool directly on the force balance equations for the velocity field on a discretized and arbitrarily deforming cortex. Since our method is based on the general force balance equations, it can easily be extended to more complex biological dependencies in terms of the constitutive laws or a dynamic coupling to a suspending fluid. We validate our algorithm by investigating the formation of a cleavage furrow on a biological cell immersed in a passive outer fluid, where we successfully compare our results to axi-symmetric simulations. We then apply our fully three-dimensional algorithm to fold formation and to study furrow formation under the influence of non-axisymmetric disturbances such as external shear. We report a reorientation mechanism by which the cell autonomously realigns its axis perpendicular to the furrow plane thus contributing to the robustness of cell division under realistic environmental conditions.

Optimized Halogen Atomic Radii for PBSA Calculations Using Off-Center Point-Charges

<div>In force field methods, the usage of off-center point-charges, also called extra-points (EPs), is a common strategy to tackle the anisotropy of the electrostatic potential of covalently-bonded halogens (X), thus allowing the description of halogen bonds (XBs) at the molecular mechanics / molecular dynamics (MM/MD) level. Diverse EP implementations exist in the literature differing on the charge sets and/or the X–EP distances. Poisson–Boltzmann and surface area (PBSA) calculations can be used to obtain solvation free energies (∆G solv ) of small molecules, often to compute binding free energies (∆G bind ) at the MM PBSA level. This method depends, among other parameters, on the empirical assignment of atomic radii (PB radii). Given the multiplicity of off-center point-charges models and the lack of specific PB radii for halogens compatible with such implementations, in this work we assessed the performance of PBSA calculations for the estimation of ∆G solv values in water (∆G hyd ), also conducting an optimization of the halogen PB radii (Cl, Br, and I) for each EP model. We not only expand the usage of EP models in the scope of the General AMBER Force Field (GAFF) but also provide the first optimized halogen PB radii in the context of the CHARMM General Force Field (CGenFF), thus contributing to improving the description of halogenated compounds in PBSA calculations.</div>

A Robust and Efficient Implicit Solvation Model for Fast Semiempirical Methods

We present a robust and efficient method to implicitly account for solvation effects in modern semiempirical quantum mechanics and force-fields. A computationally efficient yet accurate solvation model based on the analytical linearized Poisson--Boltzmann~(ALPB) model is parameterized for the extended tight binding (xTB) and density functional tight binding (DFTB) methods as well as for the recently proposed GFN-FF general force-field. The proposed methods perform well over a broad range of systems and applications, from conformational energies over transition-metal complexes to large supramolecular association reactions of charged species. For hydration free energies of small molecules GFN1-xTB(ALPB) is reaching the accuracy of sophisticated explicitly solvated approaches, with a mean absolute deviation of only 1.4 kcal/mol compared to experiment. Logarithmic octanol--water partition coefficients (log Kow) are computed with a mean absolute deviation of about 0.65 using GFN2-xTB(ALPB) compared to experimental values indicating a consistent description of differential solvent effects. Overall, more than twenty solvents for each of the six semiempirical methods are parameterized and tested. They are readily available in the xtb and dftb+ programs for diverse computational applications.

Optimized Halogen Atomic Radii for PBSA Calculations Using Off-Center Point-Charges

<div>In force field methods, the usage of off-center point-charges, also called extra-points (EPs), is a common strategy to tackle the anisotropy of the electrostatic potential of covalently-bonded halogens (X), thus allowing the description of halogen bonds (XBs) at the molecular mechanics / molecular dynamics (MM/MD) level. Diverse EP implementations exist in the literature differing on the charge sets and/or the X–EP distances. Poisson–Boltzmann and surface area (PBSA) calculations can be used to obtain solvation free energies (∆G solv ) of small molecules, often to compute binding free energies (∆G bind ) at the MM PBSA level. This method depends, among other parameters, on the empirical assignment of atomic radii (PB radii). Given the multiplicity of off-center point-charges models and the lack of specific PB radii for halogens compatible with such implementations, in this work we assessed the performance of PBSA calculations for the estimation of ∆G solv values in water (∆G hyd ), also conducting an optimization of the halogen PB radii (Cl, Br, and I) for each EP model. We not only expand the usage of EP models in the scope of the General AMBER Force Field (GAFF) but also provide the first optimized halogen PB radii in the context of the CHARMM General Force Field (CGenFF), thus contributing to improving the description of halogenated compounds in PBSA calculations.</div>

Optimized Halogen Atomic Radii for PBSA Calculations Using Off-Center Point-Charges

<div>In force field methods, the usage of off-center point-charges, also called extra-points (EPs), is a common strategy to tackle the anisotropy of the electrostatic potential of covalently-bonded halogens (X), thus allowing the description of halogen bonds (XBs) at the molecular mechanics / molecular dynamics (MM/MD) level. Diverse EP implementations exist in the literature differing on the charge sets and/or the X–EP distances. Poisson–Boltzmann and surface area (PBSA) calculations can be used to obtain solvation free energies (∆G solv ) of small molecules, often to compute binding free energies (∆G bind ) at the MM PBSA level. This method depends, among other parameters, on the empirical assignment of atomic radii (PB radii). Given the multiplicity of off-center point-charges models and the lack of specific PB radii for halogens compatible with such implementations, in this work we assessed the performance of PBSA calculations for the estimation of ∆G solv values in water (∆G hyd ), also conducting an optimization of the halogen PB radii (Cl, Br, and I) for each EP model. We not only expand the usage of EP models in the scope of the General AMBER Force Field (GAFF) but also provide the first optimized halogen PB radii in the context of the CHARMM General Force Field (CGenFF), thus contributing to improving the description of halogenated compounds in PBSA calculations.</div>

Development and Benchmarking of Open Force Field v1.0.0, the Parsley Small Molecule Force Field

We describe the structure and optimization of the Open Force Field 1.0.0 small molecule force field, code-named Parsley. Parsley uses the SMIRKS-native Open Force Field (SMIRNOFF) parameter assignment formalism in which parameter types are assigned directly by chemical perception, in contrast to traditional atom type-based approaches. This method provides a natural means to incorporate increasingly diverse chemistry without needlessly increasing force field complexity. In this work, we present essentially a full optimization of the valence parameters in the force field. The optimization was carried out with the ForceBalance tool and was informed by reference quantum chemical data that include torsion potential energy profiles, optimized gas-phase structures, and vibrational frequencies. These data were computed and are maintained with QCArchive, an open-source and freely available distributed computing and database software ecosystem. Tests of the resulting force field against compounds and data types outside the training set show improvements in optimized geometries and conformational energetics and demonstrate that Parsley's accuracy for liquid properties is similar to that of other general force fields. <br>

Development and Benchmarking of Open Force Field v1.0.0, the Parsley Small Molecule Force Field

We describe the structure and optimization of the Open Force Field 1.0.0 small molecule force field, code-named Parsley. Parsley uses the SMIRKS-native Open Force Field (SMIRNOFF) parameter assignment formalism in which parameter types are assigned directly by chemical perception, in contrast to traditional atom type-based approaches. This method provides a natural means to incorporate increasingly diverse chemistry without needlessly increasing force field complexity. In this work, we present essentially a full optimization of the valence parameters in the force field. The optimization was carried out with the ForceBalance tool and was informed by reference quantum chemical data that include torsion potential energy profiles, optimized gas-phase structures, and vibrational frequencies. These data were computed and are maintained with QCArchive, an open-source and freely available distributed computing and database software ecosystem. Tests of the resulting force field against compounds and data types outside the training set show improvements in optimized geometries and conformational energetics and demonstrate that Parsley's accuracy for liquid properties is similar to that of other general force fields. <br>