Static and Dynamic Correlations in Water: Comparison of Classical Ab Initio Molecular Dynamics at Elevated Temperature with Path Integral Simulations at Ambient Temperature.

It is a common practice in molecular dynamics (AIMD) simulations of water to use an elevated temperature to overcome the overstructuring and slow diffusion predicted by most current density functional theory (DFT) models. The simulation results obtained in this distinct thermodynamic state are then compared with experimental data at ambient temperature based on the rationale that a higher temperature effectively recovers nuclear quantum effects (NQEs) that are missing in the classical AIMD simulations. In this work, we systematically examine the foundation of this assumption for several DFT models as well as for the many-body MB-pol model.

Metrics from Wearable Devices as Candidate Predictors of Antibody Response Following Vaccination against COVID-19: Data from the Second TemPredict Study.

There is significant variability in neutralizing antibody responses (which correlate with immune protection) after COVID-19 vaccination, but only limited information is available about predictors of these responses. We investigated whether device-generated summaries of physiological metrics collected by a wearable device correlated with post-vaccination levels of antibodies to the SARS-CoV-2 receptor-binding domain (RBD), the target of neutralizing antibodies generated by existing COVID-19 vaccines. One thousand, one hundred and seventy-nine participants wore an off-the-shelf wearable device (Oura Ring), reported dates of COVID-19 vaccinations, and completed testing for antibodies to the SARS-CoV-2 RBD during the U.

Nuclear SOD1 in Growth Control, Oxidative Stress Response, Amyotrophic Lateral Sclerosis, and Cancer.

SOD1 is the major superoxide dismutase responsible for catalyzing dismutation of superoxide to hydrogen peroxide and molecular oxygen. It is well known as an essential antioxidant enzyme for maintaining cellular redox homeostasis. SOD1 dysregulation has been associated with many diseases, including amyotrophic lateral sclerosis (ALS), cancer, accelerated aging, and age-related diseases.

Alzheimer's Disease Diagnostics Using miRNA Biomarkers and Machine Learning.

Background: The current standard for Alzheimer's disease (AD) diagnosis is often imprecise, as with memory tests, and invasive or expensive, as with brain scans. However, the dysregulation patterns of miRNA in blood hold potential as useful biomarkers for the non-invasive diagnosis and even treatment of AD.

Objective: The goal of this research is to elucidate new miRNA biomarkers and create a machine-learning (ML) model for the diagnosis of AD.

DFT Calculations for Mössbauer Properties on Dinuclear Center Models of the Resting Oxidized Cytochrome c Oxidase.

Mössbauer isomer shift and quadrupole splitting properties have been calculated using the OLYP-D3(BJ) density functional method on previously obtained (W.-G. Han Du, et al.

Simplified quality assessment for small-molecule ligands in the Protein Data Bank.

More than 70% of the experimentally determined macromolecular structures in the Protein Data Bank (PDB) contain small-molecule ligands. Quality indicators of ∼643,000 ligands present in ∼106,000 PDB X-ray crystal structures have been analyzed. Ligand quality varies greatly with regard to goodness of fit between ligand structure and experimental data, deviations in bond lengths and angles from known chemical structures, and inappropriate interatomic clashes between the ligand and its surroundings.

Structural models of SARS-CoV-2 Omicron variant in complex with ACE2 receptor or antibodies suggest altered binding interfaces.

There is enormous ongoing interest in characterizing the binding properties of the SARS-CoV-2 Omicron Variant of Concern (VOC) (B.1.1.

RCSB Protein Data Bank: improved annotation, search and visualization of membrane protein structures archived in the PDB.

Motivation: Membrane proteins are encoded by approximately one fifth of human genes but account for more than half of all US FDA approved drug targets. Thanks to new technological advances, the number of membrane proteins archived in the PDB is growing rapidly. However, automatic identification of membrane proteins or inference of membrane location is not a trivial task.

RCSB Protein Data Bank resources for structure-facilitated design of mRNA vaccines for existing and emerging viral pathogens.

Structural biologists provide direct insights into the molecular bases of human health and disease. The open-access Protein Data Bank (PDB) stores and delivers three-dimensional (3D) biostructure data that facilitate discovery and development of therapeutic agents and diagnostic tools. We are in the midst of a revolution in vaccinology.

Elevating density functional theory to chemical accuracy for water simulations through a density-corrected many-body formalism.

Density functional theory (DFT) has been extensively used to model the properties of water. Albeit maintaining a good balance between accuracy and efficiency, no density functional has so far achieved the degree of accuracy necessary to correctly predict the properties of water across the entire phase diagram. Here, we present density-corrected SCAN (DC-SCAN) calculations for water which, minimizing density-driven errors, elevate the accuracy of the SCAN functional to that of "gold standard" coupled-cluster theory.

RCSB Protein Data Bank: Celebrating 50 years of the PDB with new tools for understanding and visualizing biological macromolecules in 3D.

The Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB), funded by the US National Science Foundation, National Institutes of Health, and Department of Energy, has served structural biologists and Protein Data Bank (PDB) data consumers worldwide since 1999. RCSB PDB, a founding member of the Worldwide Protein Data Bank (wwPDB) partnership, is the US data center for the global PDB archive housing biomolecular structure data. RCSB PDB is also responsible for the security of PDB data, as the wwPDB-designated Archive Keeper.

Apropos of Universal Epitope Discovery for COVID-19 Vaccines: A Framework for Targeted Phage Display-Based Delivery and Integration of New Evaluation Tools.

Targeted bacteriophage (phage) particles are potentially attractive yet inexpensive platforms for immunization. Herein, we describe targeted phage capsid display of an immunogenically relevant epitope of the SARS-CoV-2 Spike protein that is empirically conserved, likely due to the high mutational cost among all variants identified to date. This observation may herald an approach to developing vaccine candidates for broad-spectrum, towards universal, protection against multiple emergent variants of coronavirus that cause COVID-19.

Data for molecular dynamics simulations of cytochrome oxidase with the Amber force field.

Cytochrome -type quinol oxidase is an important metalloenzyme that allows many bacteria to survive in low oxygen conditions. Since oxidase is found in many prokaryotes but not in eukaryotes, it has emerged as a promising bacterial drug target. Examples of organisms containing oxidases include the bacterium that causes tuberculosis (TB) in humans, the bacterium that causes cholera, the bacterium that contributes to antibiotic resistance and sepsis, and the bacterium that causes food poisoning.

PDB-101: Educational resources supporting molecular explorations through biology and medicine.

The Protein Data Bank (PDB) archive is a rich source of information in the form of atomic-level three-dimensional (3D) structures of biomolecules experimentally determined using macromolecular crystallography, nuclear magnetic resonance (NMR) spectroscopy, and electron microscopy (3DEM). Originally established in 1971 as a resource for protein crystallographers to freely exchange data, today PDB data drive research and education across scientific disciplines. In 2011, the online portal PDB-101 was launched to support teachers, students, and the general public in PDB archive exploration (pdb101.

MB-Fit: Software infrastructure for data-driven many-body potential energy functions.

Many-body potential energy functions (MB-PEFs), which integrate data-driven representations of many-body short-range quantum mechanical interactions with physics-based representations of many-body polarization and long-range interactions, have recently been shown to provide high accuracy in the description of molecular interactions from the gas to the condensed phase. Here, we present MB-Fit, a software infrastructure for the automated development of MB-PEFs for generic molecules within the TTM-nrg (Thole-type model energy) and MB-nrg (many-body energy) theoretical frameworks. Besides providing all the necessary computational tools for generating TTM-nrg and MB-nrg PEFs, MB-Fit provides a seamless interface with the MBX software, a many-body energy and force calculator for computer simulations.

Evolution of the SARS-CoV-2 proteome in three dimensions (3D) during the first 6 months of the COVID-19 pandemic.

Understanding the molecular evolution of the SARS-CoV-2 virus as it continues to spread in communities around the globe is important for mitigation and future pandemic preparedness. Three-dimensional structures of SARS-CoV-2 proteins and those of other coronavirusess archived in the Protein Data Bank were used to analyze viral proteome evolution during the first 6 months of the COVID-19 pandemic. Analyses of spatial locations, chemical properties, and structural and energetic impacts of the observed amino acid changes in >48 000 viral isolates revealed how each one of 29 viral proteins have undergone amino acid changes.

Topology-Mediated Enhanced Polaron Coherence in Covalent Organic Frameworks.

We employ the Holstein model for polarons to investigate the relationship among defects, topology, Coulomb trapping, and polaron delocalization in covalent organic frameworks (COFs). We find that intrasheet topological connectivity and π-column density can override disorder-induced deep traps and significantly enhance polaron migration by several orders of magnitude in good agreement with recent experimental observations. The combination of percolation networks and micropores makes trigonal COFs ideally suited for charge transport followed by kagome/tetragonal and hexagonal structures.

The maternal blood lipidome is indicative of the pathogenesis of severe preeclampsia.

Preeclampsia is a pregnancy-specific syndrome characterized by hypertension and proteinuria after 20 weeks of gestation. However, it is not well understood what lipids are involved in the development of this condition, and even less is known how these lipids mediate its formation. To reveal the relationship between lipids and preeclampsia, we conducted lipidomic profiling of maternal sera of 44 severe preeclamptic and 20 healthy pregnant women from a multiethnic cohort in Hawaii.

Implications of viral infection in cancer development.

Since the identification of the first human oncogenic virus in 1964, viruses have been studied for their potential role in aiding the development of cancer. Through the modulation of cellular pathways associated with proliferation, immortalization, and inflammation, viral proteins can mimic the effect of driver mutations and contribute to transformation. Aside from the modulation of signaling pathways, the insertion of viral DNA into the host genome and the deregulation of cellular miRNAs represent two additional mechanisms implicated in viral oncogenesis.

General Many-Body Framework for Data-Driven Potentials with Arbitrary Quantum Mechanical Accuracy: Water as a Case Study.

We present a general framework for the development of data-driven many-body (MB) potential energy functions (MB-QM PEFs) that represent the interactions between small molecules at an arbitrary quantum-mechanical (QM) level of theory. As a demonstration, a family of MB-QM PEFs for water is rigorously derived from density functionals belonging to different rungs across Jacob's ladder of approximations within density functional theory (MB-DFT) and from Møller-Plesset perturbation theory (MB-MP2). Through a systematic analysis of individual MB contributions to the interaction energies of water clusters, we demonstrate that all MB-QM PEFs preserve the same accuracy as the corresponding calculations, with the exception of those derived from density functionals within the generalized gradient approximation (GGA).

Design and proof of concept for targeted phage-based COVID-19 vaccination strategies with a streamlined cold-free supply chain.

Development of effective vaccines against coronavirus disease 2019 (COVID-19) is a global imperative. Rapid immunization of the entire human population against a widespread, continually evolving, and highly pathogenic virus is an unprecedented challenge, and different vaccine approaches are being pursued. Engineered filamentous bacteriophage (phage) particles have unique potential in vaccine development due to their inherent immunogenicity, genetic plasticity, stability, cost-effectiveness for large-scale production, and proven safety profile in humans.