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Symmetry-adapted perturbation theory (SAPT) is an ab initio approach that directly computes noncovalent interaction energies in terms of electrostatics, exchange repulsion, induction/polarization, and London dispersion components. Due to its high computational scaling, routine applications of even the lowest order of SAPT are typically limited to a few hundred atoms. To address this limitation, we report here the addition of electrostatic embedding to the SAPT (EE-SAPT) and ISAPT (EE-ISAPT) methods. We illustrate the embedding scheme using water trimer as a prototype example. Then, we show that EE-SAPT/EE-ISAPT can be applied for efficiently and accurately computing noncovalent interactions in large systems, including solvated dimers and protein–ligand systems. In the latter application, particular care must be taken to properly handle the quantum mechanics/molecular mechanics boundary when it cuts covalent bonds. We investigate various schemes for handling charges near this boundary and demonstrate which are most effective in the context of charge-embedded SAPT. [ABSTRACT FROM AUTHOR]

The development of reliable and extensible molecular mechanics (MM) force fields-fast, empirical models characterizing the potential energy surface of molecular systems-is indispensable for biomolecular simulation and computer-aided drug design. Here, we introduce a generalized and extensible machine-learned MM force field, espaloma-0.3, and an end-to-end differentiable framework using graph neural networks to overcome the limitations of traditional rule-based methods. Trained in a single GPU-day to fit a large and diverse quantum chemical dataset of over 1.1 M energy and force calculations, espaloma-0.3 reproduces quantum chemical energetic properties of chemical domains highly relevant to drug discovery, including small molecules, peptides, and nucleic acids. Moreover, this force field maintains the quantum chemical energy-minimized geometries of small molecules and preserves the condensed phase properties of peptides and folded proteins, self-consistently parametrizing proteins and ligands to produce stable simulations leading to highly accurate predictions of binding free energies. This methodology demonstrates significant promise as a path forward for systematically building more accurate force fields that are easily extensible to new chemical domains of interest., Competing Interests: J. D. C. is a current member of the Scientific Advisory Board of OpenEye Scientific Software, Redesign Science, Ventus Therapeutics, and Interline Therapeutics, and has equity interests in Redesign Science and Interline Therapeutics. The Chodera laboratory receives or has received funding from multiple sources, including the National Institutes of Health, the National Science Foundation, the Parker Institute for Cancer Immunotherapy, Relay Therapeutics, Entasis Therapeutics, Silicon Therapeutics, EMD Serono (Merck KGaA), AstraZeneca, Vir Biotechnology, Bayer, XtalPi, Interline Therapeutics, the Molecular Sciences Software Institute, the Starr Cancer Consortium, the Open Force Field Consortium, Cycle for Survival, a Louis V. Gerstner Young Investigator Award, and the Sloan Kettering Institute. A complete funding history for the Chodera lab can be found at http://choderalab.org/funding. Y. W. has limited financial interests in Flagship Pioneering, Inc. and its subsidiaries. M. R. S. is an Open Science Fellow with Psivant Sciences and consults for Relay Therapeutics. D. L. M. serves on the scientific advisory boards of Anagenex and OpenEye Scientific Software, Cadence Molecular Sciences, and is an Open Science Fellow with Psivant., (This journal is © The Royal Society of Chemistry.)

The Radar for Europa Assessment and Sounding: Ocean to Near-surface (REASON) is a dual-frequency ice-penetrating radar (9 and 60 MHz) onboard the Europa Clipper mission. REASON is designed to probe Europa from exosphere to subsurface ocean, contributing the third dimension to observations of this enigmatic world. The hypotheses REASON will test are that (1) the ice shell of Europa hosts liquid water, (2) the ice shell overlies an ocean and is subject to tidal flexing, and (3) the exosphere, near-surface, ice shell, and ocean participate in material exchange essential to the habitability of this moon. REASON will investigate processes governing this material exchange by characterizing the distribution of putative non-ice material (e.g., brines, salts) in the subsurface, searching for an ice-ocean interface, characterizing the ice shell's global structure, and constraining the amplitude of Europa's radial tidal deformations. REASON will accomplish these science objectives using a combination of radar measurement techniques including altimetry , reflectometry , sounding , interferometry , plasma characterization , and ranging . Building on a rich heritage from Earth, the moon, and Mars, REASON will be the first ice-penetrating radar to explore the outer solar system. Because these radars are untested for the icy worlds in the outer solar system, a novel approach to measurement quality assessment was developed to represent uncertainties in key properties of Europa that affect REASON performance and ensure robustness across a range of plausible parameters suggested for the icy moon. REASON will shed light on a never-before-seen dimension of Europa and - in concert with other instruments on Europa Clipper - help to investigate whether Europa is a habitable world., Competing Interests: Competing InterestsThe authors have no competing interests to declare that are relevant to the content of this article., (© The Author(s) 2024.)

Background: The widespread physical, mental, and emotional health impacts of trauma are well established. Trauma-informed care (TIC) is an approach that uses knowledge about trauma and its effects to create safe care environments., Purpose: Using a concurrent mixed-methods design, this study assessed faculty, preceptor, and students' perceptions about the need for TIC content in nursing education., Methods: Semistructured interviews were conducted with 15 faculty, and cross-sectional survey data were collected from a nonprobability sample of 99 nursing students at a large Midwestern university to evaluate the need for education on TIC., Results: Faculty and preceptors stressed the importance of education on TIC and discussed barriers and facilitators to implementation. Nursing students reported that it is important to learn about TIC, yet do not feel prepared to provide TIC., Conclusions: The results illustrate the need for nursing content on TIC and provide recommendations for trauma-informed educational practices., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)