One Health as a Core Component of Veterinary Medicine: Defining Day-1 Public Health Competencies for the Veterinary Workforce.

Animal health and veterinary medicine are integral to One Health, contributing important perspectives on complex challenges arising at the human-animal-environment interface. The published Competency-Based Veterinary Education (CBVE) framework dedicates a domain of competence and three associated sub-competencies to public health (Domain 4). However, a panel of One Health scientists sought to establish additional outcomes believed necessary to support core veterinary curricula related to veterinary public health (VPH)/One Health.

A new method to calculate broadband dielectric spectra of solvents from molecular dynamics simulations demonstrated with polarizable force fields.

Simulating the dielectric spectra of solvents requires the nuanced definition of inter- and intra-molecular forces. Non-polarizable force fields, while thoroughly benchmarked for dielectric applications, do not capture all the spectral features of solvents, such as water. Conversely, polarizable force fields have been largely untested in the context of dielectric spectroscopy but include charge and dipole fluctuations that contribute to intermolecular interactions.

Survey of antimicrobial and probiotic use practices in wildlife rehabilitation in the United States.

Antimicrobial resistance is a global health concern. As such, there have been increased efforts to monitor and standardize antimicrobial prescribing practices in humans and domestic animals. In contrast, there is relatively little known about specific prescribing practices in wild animals despite the wide use of antimicrobials and other microbial interventions, such as probiotics to treat captive wildlife.

Force Field X: A computational microscope to study genetic variation and organic crystals using theory and experiment.

Force Field X (FFX) is an open-source software package for atomic resolution modeling of genetic variants and organic crystals that leverages advanced potential energy functions and experimental data. FFX currently consists of nine modular packages with novel algorithms that include global optimization via a many-body expansion, acid-base chemistry using polarizable constant-pH molecular dynamics, estimation of free energy differences, generalized Kirkwood implicit solvent models, and many more. Applications of FFX focus on the use and development of a crystal structure prediction pipeline, biomolecular structure refinement against experimental datasets, and estimation of the thermodynamic effects of genetic variants on both proteins and nucleic acids.

Beyond isotropic repulsion: Classical anisotropic repulsion by inclusion of p orbitals.

Accurate modeling of intermolecular repulsion is an integral component in force field development. Although repulsion can be explicitly calculated by applying the Pauli exclusion principle, this approach is computationally viable only for systems of limited sizes. Instead, it has previously been shown that repulsion can be reformulated in a "classical" picture: the Pauli exclusion principle prohibits electrons from occupying the same state, leading to a depletion of electronic charge between atoms, giving rise to an enhanced nuclear-nuclear electrostatic repulsion.

Constant-pH Simulations with the Polarizable Atomic Multipole AMOEBA Force Field.

Accurately predicting protein behavior across diverse pH environments remains a significant challenge in biomolecular simulations. Existing constant-pH molecular dynamics (CpHMD) algorithms are limited to fixed-charge force fields, hindering their application to biomolecular systems described by permanent atomic multipoles or induced dipoles. This work overcomes these limitations by introducing the first polarizable CpHMD algorithm in the context of the Atomic Multipole Optimized Energetics for Biomolecular Applications (AMOEBA) force field.

A generalized Kirkwood implicit solvent for the polarizable AMOEBA protein model.

Computational simulation of biomolecules can provide important insights into protein design, protein-ligand binding interactions, and ab initio biomolecular folding, among other applications. Accurate treatment of the solvent environment is essential in such applications, but the use of explicit solvents can add considerable cost. Implicit treatment of solvent effects using a dielectric continuum model is an attractive alternative to explicit solvation since it is able to describe solvation effects without the inclusion of solvent degrees of freedom.

Elucidating Design Rules toward Enhanced Solid-State Charge Transport in Oligoether-Functionalized Dioxythiophene-Based Alternating Copolymers.

This study investigates the solid-state charge transport properties of the oxidized forms of dioxythiophene-based alternating copolymers consisting of an oligoether-functionalized 3,4-propylenedioxythiophene (ProDOT) copolymerized with different aryl groups, dimethyl ProDOT (DMP), 3,4-ethylenedioxythiophene (EDOT), and 3,4-phenylenedioxythiophene (PheDOT), respectively, to yield copolymers P(OE3)-D, P(OE3)-E, and P(OE3)-Ph. At a dopant concentration of 5 mM FeTos, the electrical conductivities of these copolymers vary significantly (ranging between 9 and 195 S cm) with the EDOT copolymer, P(OE3)-E, achieving the highest electrical conductivity. UV-vis-NIR and X-ray spectroscopies show differences in both susceptibility to oxidative doping and extent of oxidation for the P(OE3) series, with P(OE3)-E being the most doped.

Quantifying Charge Carrier Localization in PBTTT Using Thermoelectric and Spectroscopic Techniques.

Chemically doped poly[2,5-bis(3-alkylthiophen-2-yl)thieno[3,2-]thiophene] (PBTTT) shows promise for many organic electronic applications, but rationalizing its charge transport properties is challenging because conjugated polymers are inhomogeneous, with convoluted optical and solid-state transport properties. Herein, we use the semilocalized transport (SLoT) model to quantify how the charge transport properties of PBTTT change as a function of iron(III) chloride (FeCl) doping level. We use the SLoT model to calculate fundamental transport parameters, including the carrier density needed for metal-like electrical conductivities and the position of the Fermi energy level with respect to the transport edge.

Role of aggregates and microstructure of mixed-ionic-electronic-conductors on charge transport in electrochemical transistors.

Synthetic efforts have delivered a library of organic mixed ionic-electronic conductors (OMIECs) with high performance in electrochemical transistors. The most promising materials are redox-active conjugated polymers with hydrophilic side chains that reach high transconductances in aqueous electrolytes due to volumetric electrochemical charging. Current approaches to improve transconductance and device stability focus mostly on materials chemistry including backbone and side chain design.

Accurate Host-Guest Binding Free Energies Using the AMOEBA Polarizable Force Field.

A grand challenge of computational biophysics is accurate prediction of interactions between molecules. Molecular dynamics (MD) simulations have recently gained much interest as a tool to directly compute rigorous intermolecular binding affinities. The choice of a fixed point-charge or polarizable multipole force field used in MD is a topic of ongoing discussion.

Advances in the Synthesis of Preceramic Polymers for the Formation of Silicon-Based and Ultrahigh-Temperature Non-Oxide Ceramics.

Preceramic polymers (PCPs) are a group of specialty macromolecules that serve as precursors for generating inorganics, including ceramic carbides, nitrides, and borides. PCPs represent interesting synthetic challenges for chemists due to the elements incorporated into their structure. This group of polymers is also of interest to engineers as PCPs enable the processing of polymer-derived ceramic products including high-performance ceramic fibers and composites.

Metal-like Charge Transport in PEDOT(OH) Films by Post-processing Side Chain Removal from a Soluble Precursor Polymer.

Herein, a route to produce highly electrically conductive doped hydroxymethyl functionalized poly(3,4-ethylenedioxythiophene) (PEDOT) films, termed PEDOT(OH) with metal-like charge transport properties using a fully solution processable precursor polymer is reported. This is achieved via an ester-functionalized PEDOT derivative [PEDOT(EHE)] that is soluble in a range of solvents with excellent film-forming ability. PEDOT(EHE) demonstrates moderate electrical conductivities of 20-60 S cm and hopping-like (i.

Classical Exchange Polarization: An Anisotropic Variable Polarizability Model.

Polarizability, or the tendency of the electron distribution to distort under an electric field, often depends on the local chemical environment. For example, the polarizability of a chloride ion is larger in gas phase compared to a chloride ion solvated in water. This effect is due to the restriction the Pauli exclusion principle places on the allowed electron states.

Computationally driven discovery of SARS-CoV-2 M inhibitors: from design to experimental validation.

We report a fast-track computationally driven discovery of new SARS-CoV-2 main protease (M) inhibitors whose potency ranges from mM for the initial non-covalent ligands to sub-μM for the final covalent compound (IC = 830 ± 50 nM). The project extensively relied on high-resolution all-atom molecular dynamics simulations and absolute binding free energy calculations performed using the polarizable AMOEBA force field. The study is complemented by extensive adaptive sampling simulations that are used to rationalize the different ligand binding poses through the explicit reconstruction of the ligand-protein conformation space.

Mapping Mechanistic Pathways of Acute Oral Systemic Toxicity Using Chemical Structure and Bioactivity Measurements.

Regulatory agencies around the world have committed to reducing or eliminating animal testing for establishing chemical safety. Adverse outcome pathways can facilitate replacement by providing a mechanistic framework for identifying the appropriate non-animal methods and connecting them to apical adverse outcomes. This study separated 11,992 chemicals with curated rat oral acute toxicity information into clusters of structurally similar compounds.

Significant Enhancement of the Electrical Conductivity of Conjugated Polymers by Post-Processing Side Chain Removal.

The processability and electronic properties of conjugated polymers (CPs) have become increasingly important due to the potential of these materials in redox and solid-state devices for a broad range of applications. To solubilize CPs, side chains are needed, but such side chains reduce the relative fraction of electroactive material in the film, potentially obstructing π-π intermolecular interactions, localizing charge carriers, and compromising desirable optoelectronic properties. To reduce the deleterious effects of side chains, we demonstrate that post-processing side chain removal, exemplified here via ester hydrolysis, significantly increases the electrical conductivity of chemically doped CP films.

Polarizable Water Potential Derived from a Model Electron Density.

A new empirical potential for efficient, large scale molecular dynamics simulation of water is presented. The HIPPO (Hydrogen-like Intermolecular Polarizable POtential) force field is based upon the model electron density of a hydrogen-like atom. This framework is used to derive and parametrize individual terms describing charge penetration damped permanent electrostatics, damped polarization, charge transfer, anisotropic Pauli repulsion, and damped dispersion interactions.

Antitumor properties of novel sesquiterpene lactone analogs as NFκB inhibitors that bind to the IKKβ ubiquitin-like domain (ULD).

Melampomagnolide B (MMB, 3) is a parthenolide (PTL, 1) based sesquiterpene lactone that has been used as a template for the synthesis of a plethora of lead anticancer agents owing to its reactive C-10 primary hydroxyl group. Such compounds have been shown to inhibit the IKKβ subunit, preventing phosphorylation of the cytoplasmic IκB inhibitory complex. The present study focuses on the synthesis and in vitro antitumor properties of novel benzyl and phenethyl carbamates of MMB (7a-7k).

An Electroactive Oligo-EDOT Platform for Neural Tissue Engineering.

The unique electrochemical properties of the conductive polymer poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) make it an attractive material for use in neural tissue engineering applications. However, inadequate mechanical properties, and difficulties in processing and lack of biodegradability have hindered progress in this field. Here, the functionality of PEDOT:PSS for neural tissue engineering is improved by incorporating 3,4-ethylenedioxythiophene (EDOT) oligomers, synthesized using a novel end-capping strategy, into block co-polymers.

Implicit Solvents for the Polarizable Atomic Multipole AMOEBA Force Field.

Computational protein design, ab initio protein/RNA folding, and protein-ligand screening can be too computationally demanding for explicit treatment of solvent. For these applications, implicit solvent offers a compelling alternative, which we describe here for the polarizable atomic multipole AMOEBA force field based on three treatments of continuum electrostatics: numerical solutions to the nonlinear and linearized versions of the Poisson-Boltzmann equation (PBE), the domain-decomposition conductor-like screening model (ddCOSMO) approximation to the PBE, and the analytic generalized Kirkwood (GK) approximation. The continuum electrostatics models are combined with a nonpolar estimator based on novel cavitation and dispersion terms.