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Sickle cell disease, a highly debilitating disease affecting millions worldwide, is caused by the homozygous inheritance of the mutant haemoglobin S (HbS), a malaria-stabilized gene conferring protection against lethal cerebral malaria. When sickle red blood cells traverse deoxygenated bloodstreams, HbS rapidly nucleates into polymers that keep the sickle cell Piezo1 channels open for the duration of deoxy transits. On transition to oxy streams, Piezo1 channels close immediately and remain closed.

Accurate prediction of nuclear magnetic resonance (NMR) relaxation parameters from molecular dynamics (MD) simulation trajectories is essential for quantitatively linking atomistic-scale motions to experimental observables. Here, we introduce MD2NMR, an open-source Python framework for calculating longitudinal (R1) and transverse (R2) relaxation rates, as well as rotational correlation times (τc), directly from atomistic MD trajectories. The framework implements efficient algorithms for evaluating the internuclear vector time correlation functions, spectral density functions, and their frequency-dependent components, with explicit treatment of both global and internal motions.

The lymphocyte oriented kinase (LOK, also known as STK10) is a critical regulator of membrane tension, and an important oncogenic target that mediates the epithelial-to-mesenchymal transition. LOK regulates membrane dynamics through phosphorylation of ezrin/radixin/moesin (ERM) domain proteins, but the molecular mechanisms through which LOK is able to target to its substrate are yet unknown. Here, we show that LOK and ezrin colocalize at the apical surface of epithelial cells via the LOK C-terminal domain (LOK-CTD).

Rhodopsin is a retinal protein and a G-protein coupled receptor that is critical for vertebrate vision. Extensive crystallization efforts of rhodopsin since the publication of its first structure in 2000 have generated 66 entries in the protein databank of different conformational states of rhodopsin with and without its binding partners arrestin, rhodopsin kinase, and the G-protein, transducin. This provides us with an opportunity to quantify the interactions of retinal with rhodopsin in different conformations at a large scale.

LignAmb25 is a comprehensive force field for lignin molecular dynamics simulations implemented natively within the AMBER package. The force field includes parameters for all common monolignol units (p-coumaryl, coniferyl, caffeyl, and sinapyl alcohol) and their associated linkages (β-O4, β-5, β-β, β-1, 5-5, 5-O4, α-O4, BDO, and DBDO), along with less commonly encountered units such as tricin, spirodienones, and hydroxystilbenes. This enables simulations of both softwood and hardwood lignin structures with compositions that would be difficult to isolate experimentally.

The structures of membrane proteins, such as the C99 dimer, are commonly resolved using protein nuclear magnetic resonance (NMR), which employs micelles as membrane mimics. Protein NMR is not able to determine the aggregation numbers of micelles, however, and while several experimental techniques exist for quantifying the aggregation numbers of pure micelles, these are generally not applied to micelle-encapsulated proteins. Molecular dynamics simulations of the C99 dimer and other transmembrane proteins have been performed to complement micelle-phase protein structure studies.

Accurate RNA 3D structure evaluation on candidates is critical for accurate RNA 3D structure predictions. Although some knowledge-based potentials and scoring functions have been developed for RNA 3D structure evaluation, their performance still remains rather limited, especially for the challenging datasets from RNA 3D structure prediction methods. In this work, we developed TriRNASP, an efficient statistical potential with three-body effects, aiming for accurate RNA 3D structure evaluation. TriRNASP integrates coarse-grained three-body correlations with Kullback-Leibler divergence and atom clash penalty.

Extracellular vesicles (EVs) mediate critical intercellular communication, yet the molecular mechanisms that govern multivesicular endosome (MVE) fusion with the plasma membrane and exosome release remain poorly understood. Phospholipase D1 (PLD1) produces phosphatidic acid (PA), a lipid involved in membrane remodeling, but when and how PLD1 and PA act during exosome secretion has not been defined. Here, we used immunofluorescence and total internal reflection fluorescence microscopy (TIRFM) to track individual CD63+ MVEs together with fluorescent PLD1 or a PA reporter (GFP-PASS) in A549 cells.

Membrane lipid composition varies significantly across organisms, cell types, and organelles. Mammalian membranes predominantly contain lipids like phosphatidylcholine or sphingomyelin, whereas bacterial membranes are rich in phosphatidylglycerol, phosphatidylethanolamine, and cardiolipin. This diversity in lipid composition presents an opportunity to design peptides that target specific cell types. Particularly, peptides designed to preferentially bind bacterial membranes can have applications to treat bacterial infections while avoiding toxicity.

Premature ventricular contractions (PVCs) are abnormal heartbeats that can trigger life-threatening arrhythmias. One mechanism responsible for PVCs is triggered activity. In this process, spontaneous calcium (Ca2+) release from the sarcoplasmic reticulum, and subsequent Ca2+ waves at the subcellular level promote transient inward currents that lead to delayed afterdepolarizations at the cellular level. In uniform, healthy tissue, such events are often benign because the surrounding healthy cells act as an electrical sink, suppressing the abnormal signals from a few pathological source cells.

RNA-binding proteins form biomolecular condensates with RNA through phase separation, playing crucial roles in various cellular processes. While intrinsically disordered regions (IDRs) are key drivers of phase separation, additional factors such as folded domains and RNA also influence condensate formation and physical properties. However, the molecular mechanisms underlying this regulation remain elusive. Here, using molecular dynamics simulations, we investigate how the multidomain structure of TDP-43, which consists of its IDR, RNA recognition motifs (RRMs), and N-terminal domain (NTD), interacts with RNA and affects the characteristics of phase separation.

Deciphering the mechanisms of protein-protein interactions (PPIs) and protein structural changes within the native cellular environment is crucial for advancing drug discovery. In-vivo chemical cross-linking coupled with mass spectrometry (XL-MS) captures weak, transient and higher-order interactions that are often dysregulated under altered physiological conditions and remain challenging to detect using conventional methods. Applications of in-vivo XL-MS range from targeted mapping of PPIs to large-scale identification of interactome networks within the cells.