Conotoxin Prediction: New Features to Increase Prediction Accuracy.

Conotoxins are toxic, disulfide-bond-rich peptides from cone snail venom that target a wide range of receptors and ion channels with multiple pathophysiological effects. Conotoxins have extraordinary potential for medical therapeutics that include cancer, microbial infections, epilepsy, autoimmune diseases, neurological conditions, and cardiovascular disorders. Despite the potential for these compounds in novel therapeutic treatment development, the process of identifying and characterizing the toxicities of conotoxins is difficult, costly, and time-consuming.

Integrative structural studies of the SARS-CoV-2 spike protein during the fusion process (2022).

SARS-CoV-2 is the virus responsible for the COVID-19 pandemic and catastrophic, worldwide health and economic impacts. The spike protein on the viral surface is responsible for viral entry into the host cell. The binding of spike protein to the host cell receptor ACE2 is the first step leading to fusion of the host and viral membranes.

Conformational control sequence for a heteropeptoid in water: coupled NMR and Rosetta modelling.

We report a critical advance in the generation and characterization of peptoid hetero-oligomers. A library of sub-monomers with amine and carboxylate side-chains are combined in different sequences using microwave-assisted synthesis. Their sequence-structure propensity is confirmed by circular dichroism, and conformer subtypes are enumerated by NMR.

Modeling the NP-vRNA-Polymerase Complex in Atomic Detail.

Seasonal flu is an acute respiratory disease that exacts a massive toll on human populations, healthcare systems and economies. The disease is caused by an enveloped virus containing eight ribonucleoprotein (RNP) complexes. Each RNP incorporates multiple copies of nucleoprotein (NP), a fragment of the viral genome (vRNA), and a viral RNA-dependent RNA polymerase (POL), and is responsible for packaging the viral genome and performing critical functions including replication and transcription.

Concentration-dependent and configuration-dependent interactions of monovalent ions with an RNA tetraloop.

Monovalent salt solutions have strongly coupled interactions with biopolymers, from large polyelectrolytes to small RNA oligomers. High salt concentrations have been known to induce transitions in the structure of RNA, producing non-canonical configurations and even driving RNA to precipitate out of solution. Using all-atom molecular dynamics simulations, we model a monovalent salt species (KCL) at high concentrations (0.

Structural Transition and Antibody Binding of EBOV GP and ZIKV E Proteins from Pre-Fusion to Fusion-Initiation State.

Membrane fusion proteins are responsible for viral entry into host cells—a crucial first step in viral infection. These proteins undergo large conformational changes from pre-fusion to fusion-initiation structures, and, despite differences in viral genomes and disease etiology, many fusion proteins are arranged as trimers. Structural information for both pre-fusion and fusion-initiation states is critical for understanding virus neutralization by the host immune system.

Equilibrium Denaturation and Preferential Interactions of an RNA Tetraloop with Urea.

Urea is an important organic cosolute with implications in maintaining osmotic stress in cells and differentially stabilizing ensembles of folded biomolecules. We report an equilibrium study of urea-induced denaturation of a hyperstable RNA tetraloop through unbiased replica exchange molecular dynamics. We find that, in addition to destabilizing the folded state, urea smooths the RNA free energy landscape by destabilizing specific configurations, and forming favorable interactions with RNA nucleobases.

Free-energy landscape of a hyperstable RNA tetraloop.

We report the characterization of the energy landscape and the folding/unfolding thermodynamics of a hyperstable RNA tetraloop obtained through high-performance molecular dynamics simulations at microsecond timescales. Sampling of the configurational landscape is conducted using temperature replica exchange molecular dynamics over three isochores at high, ambient, and negative pressures to determine the thermodynamic stability and the free-energy landscape of the tetraloop. The simulations reveal reversible folding/unfolding transitions of the tetraloop into the canonical A-RNA conformation and the presence of two alternative configurations, including a left-handed Z-RNA conformation and a compact purine Triplet.

Psychologists in medical schools and academic medical centers: over 100 years of growth, influence, and partnership.

Psychologists have served on the faculties of medical schools for over 100 years. Psychologists serve in a number of different roles and make substantive contributions to medical schools' tripartite mission of research, education, and clinical service. This article provides an overview of the history of psychologists' involvement in medical schools, including their growing presence in and integration with diverse departments over time.

Board certification in psychology: insights from medicine and hospital psychology.

For physicians board certification is an accepted tradition that research suggests improves services and outcomes. In contrast, relatively few psychologists pursue board certification suggesting ambivalence or limited contingencies reinforcing it. The authors report on medical school and hospital-based psychologists' attitudes toward board certification and current certification status.

Hospital privileges for psychologists in the era of competencies and increased accountability.

After campaigning to be granted hospital privileges decades ago, new issues are emerging that are affecting psychologists' hospital privileges. Some of the forces shaping hospital privileges emanate from within the field of psychology, where there has been a movement to more closely examine psychologists' competences. Other forces impinging on hospital privileges are external to psychology, most notably the Joint Commission, which has promulgated new standards for hospital-based practitioners across disciplines.