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There are a large class of enveloped viruses that utilize sophisticated fusion mechanisms as a precursor to enter host cells. In SARS-Cov-2 the S2 domain of the S protein contains the fusion peptide (FP), which is believed to be central to the inter-membrane fusion machinery. However, the microscopic parameters that drive enhanced fusogenicity of the SARS-CoV-2 FP on realistic complex cellular membranes, leading to the observed virulence and fatality due to SARS-CoV-2 infection remains unclear. In this report, we identify the correlation between SARS-CoV-2 FP conformational and multi-phase cellular membrane dynamical heterogeneity, using existing and new membranotropic parameters, that drives enhanced SARS-CoV-2 FP fusogenicity.

Epithelial tissues are often exposed to cyclic deformations in their physiological environment. Maintenance of mechanical integrity relies on intercellular adhesion proteins which link neighbouring cells and transmit forces across the cellular network. The stability of these intercellular adhesion complexes is therefore critical for tissue strength. Under sustained stress, failure of intercellular adhesion complexes leads to damage accumulation that progressively weakens the material and ultimately causes failure at the tissue scale.

Accumulation of amyloid-β (Aβ) peptides and Tau proteins in the brain is a hallmark of neurodegeneration. Such build-up forms Aβ plaques and Tau neurofibrillary tangles, both of which are associated with synaptic loss, cognitive decline, and reduced cerebral blood flow in Alzheimer’s disease (AD). Two ion channels in brain capillary endothelial cells (ECs)—the inwardly rectifying potassium channel Kir2.1 and the mechanosensitive channel Piezo1—are critical regulators of cerebral blood flow, and both display impaired activity in AD.

Viral capsids are metastable assemblies whose large-scale dynamics enable critical steps in infection, including the exposure of internal protein segments that interact with host membranes. Resolving the mechanisms underlying these transitions remains challenging because they involve rare, cooperative motions distributed across entire viral particles. Here, we develop a full-capsid structure-based molecular dynamics framework to investigate infection-relevant dynamics in the T=3 Flock House virus capsid, a model non-enveloped RNA virus.

The frameshifting stimulatory element (FSE) of SARS-CoV-2 regulates programmed −1 ribosomal frameshifting, a process critical for viral protein synthesis, which has garnered attention as a potential antiviral target. In SARS-CoV-2, a 3-stem H-type pseudoknot has been widely recognized as the primary structure stimulating −1 frameshifting. However, both experimental and computational studies have revealed that the FSE is structurally heterogeneous and can adopt alternative structures. While this conformational plasticity is believed to play a central role in modulating frameshifting efficiency, transition pathways between these alternative FSE structures have remained poorly understood.

Predicting favorable protein-peptide binding events remains a central challenge in biophysics, with continued uncertainty surrounding how nonlocal effects shape the global energy landscape. Here, we introduce peripheral surface information (PSI) entropy, SΨ, a quantitative measure of the statistical variability in apolar and charged non-interacting surface (NIS) proportions across conformational ensembles. Within the Gibbs free-energy relation ΔG = ΔH − TΔS, SΨ is proposed as a computationally tractable entropic proxy rather than a direct thermodynamic observable or stand-alone estimator of binding affinity.

The motor protein kinesin moves over the microtubule (MT) by undergoing a motility cycle involving MT-bound and unbound states. Compared to the structurally well-defined MT-bound state, very little is known about the behaviors of kinesin in the unbound state at the atomistic-level. In order to maintain motility, the unbound head hovers near the MT, where the near-range interaction remains undefined. To this end, we perform a total of over 82-μs all-atom molecular dynamics simulations of a Kinesin-1 motor head detaching and hovering over the MT lattice by using the Anton-2 supercomputer.

Kinesin-5 motor proteins play a vital role in mitotic spindle formation by generating essential forces during cell division that are necessary for proper chromosome segregation. Previous studies have confirmed the fundamental role of direct binding interactions between the tail and motor domains in kinesin-5-driven microtubule sliding. Post-translational modifications have emerged as an effective strategy for regulating the activity and structure of kinesin-5 motor proteins. Tail phosphorylation at nine mitotic residues has been suggested as a key regulatory mechanism for kinesin-5.

Ionizable aminolipids enable lipid nanoparticles (LNPs) to encapsulate nucleic acids at neutral pH and to release their cargo upon endosomal acidification. The discrepancy between this effective, acidic LNP pKa and the basic intrinsic pKa of aminolipids, however, remains poorly understood.Here, we performed microsecond constant-pH molecular dynamics simulations of five widely used aminolipids (DODAP, DLin-MC3-DMA, DLin-KC2-DMA, ALC-0315, and SM-102) embedded in different LNP-relevant ternary DOPC/DSPC–cholesterol membranes to quantify how aminolipid structure and membrane composition jointly govern aminolipid protonation and the associated pH-dependent membrane remodeling.

Self-labeling protein tags (SLPs) enable protein-specific conjugation of synthetic fluorophores for versatile bioimaging, yet their rational engineering has largely relied on static structural models. Here, we reveal that crystal structures of SLP-dye complexes generally bear packing artifacts due to strong π-π interactions of dyes, frequently failing to profile the chromophore microenvironment. By integrating molecular dynamics (MD) with crystallography, we elucidate distinct dynamic behaviors of fluorophores across major SLPs: quasi-free diffusion in SNAP-tag, balanced hydrophobic-polar interactions in TMP-tag, and discrete, state-selective anchoring in HaloTag and Rho-tag.

RyR2 channels regulate Ca2+ release from the sarcoplasmic reticulum (SR), the Ca storage organelle in cardiac muscle. Altered RyR2 activity is a key factor promoting atrial and ventricular Ca- arrhythmias, but it is unclear how changes in RyR2 open probability underlie a sustained pro- or anti-arrhythmic affect against a background of “autoregulation” whereby SR load adjusts until the RyR2 Ca2+ leak once again balances Ca2+ uptake by SERCA2a. Accordingly, tetracaine, a closed channel blocker that increases RyR2 closed durations, increases SR Ca2+ load and promotes Ca2+ waves in CSQ knockout cells.

A packed community of exponentially proliferating microbes will spread in size exponentially. However, due to nutrient depletion, mechanical constraints, or other limitations, exponential proliferation is not indefinite, and the spreading slows. Here, we theoretically explore a fundamental question: is it possible to infer the dominant limitation type from the spreading dynamics? Using a continuum active fluid model, we consider three limitations to cell proliferation: intrinsic growth arrest (e.g., due to sporulation), pressure from other cells, and nutrient access.