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Proper assembly of collagen fibrils is essential as they constitute a plurality of protein mass and structure in extracellular matrices. However, the molecular determinants of the collagen fibrillization mechanism are difficult to characterize in part due to the size and heterogeneity of the collagen triple helix. We have used MD simulations to characterize the dimerization free energy landscape of model collagen mimetic peptide triple helices. Under in vivo buffer conditions we find that domains consisting purely of Proline-Hydroxyproline-Glycine (POG) repeats readily dimerize via a tight hydrophobic association stabilized via additional hydrogen bonds between Hydroxyprolines (Hyp).

Protein function emerges from the dynamic interplay between structural organization, environmental factors, and thermal fluctuations. This complex choreography governs essential biological processes from enzymatic catalysis to signal transduction. Extracting the underlying mechanics from atomistic simulations, however, remains a central challenge. Current computational approaches face a fundamental trade-off: variance-based methods like Principal Component Analysis (PCA) identify high-amplitude motions but do not resolve the governing forces, while mechanics-based Elastic Network Models (ENMs) are interpretable but neglect crucial environmental effects from solvent and cofactors.

Autophosphorylation of CheA is key to initiation of the phosphorylation cascade that eventually controls the direction of downstream flagellar motors for chemotaxis signaling in motile bacteria. The phospho-transfer reaction, from ATP bound in the P4 catalytic domain to a specific His residue in the P1 substrate domain in CheA, can be significantly accelerated within core signaling unit complexes containing chemoreceptors, CheA and CheW. Previous studies have proposed that CheA autophosphorylation activity is regulated by changing the dynamics of P4 and/or altering its interactions with P1 in response to signals transmitted from chemoreceptors.

Pump-Leak (P-L) models are powerful tools in membrane and cell physiology, providing a quantitative framework to understand how cells regulate intracellular ion concentrations, volume and membrane potential, via ion transport mechanisms. However, constructing a P-L model for a specific cell type is challenging, because it requires numerous cell-specific parameters, many of which are experimentally inaccessible. Here we present a Linear Programming (LP)-based method to estimate such inaccessible parameters, using only a subset of experimentally determined values.

The carboxy-terminal domain (CTD) of RNA Polymerase II, composed of tandem heptad repeats with the consensus sequence YSPTSPS, orchestrates the transcription cycle through a dynamic series of post-translational modifications. Among these, the phosphorylation of Ser5 is critical for initiator/promoter clearance and the recruitment of capping enzymes. However, the exact conformational consequences of these modifications are still not fully understood. This study investigates how Ser5 phosphorylation affects the local and global conformation of the CTD, its influence on proline isomerization, and how variations in the repeat sequence modulate these effects.

The spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mediates viral entry by binding its receptor-binding domain (RBD) to the host receptor ACE2. Spike mutations in different variants have been experimentally shown to influence the rate of conformational transitions and alter viral infectivity. In parallel, both experimental and computational studies have reported the presence of long-range allosteric communication within the spike protein, suggesting that such mutations may also affect allosteric signaling pathways involved in viral function.

IM30, the inner membrane-associated protein of 30 kDa, conserved in cyanobacteria and chloroplasts, is a member of the ESCRT-III superfamily of membrane remodeling proteins. Like other ESCRT-III proteins, IM30 forms higher-order oligomeric structures, although the mechanisms regulating its assembly and disassembly remain poorly understood. A hallmark of ESCRT-III protein monomers is the presence of at least five α-helices, with the long helices α1 and α2/3 forming a helical hairpin that constitutes the structural core of all superfamily members.

Time-resolved X-ray solution scattering (TR-XSS) studies provide experimental probes of transient conformational states in macromolecules. Difference X-ray scattering curves from integral membrane proteins are predicted to be influenced by the presence of the surrounding detergent micelle. Here we present time-dependent X-ray solution scattering data from visual rhodopsin when solubilized in two different detergents: the nonionic surfactant n-dodecyl-β-D-maltoside (DDM) and the zwitterionic detergent 3-[(3-cholamidopropyl) dimethylammonio]-1-propanesulfonate (CHAPS).

Clathrin-mediated endocytosis (CME) is an important internalization route for macromolecules, lipids, and membrane receptors in eukaryotic cells. During CME, the plasma membrane invaginates and pinches off to form clathrin-coated vesicles (CCVs). This rapid, nanoscale process involves significant changes to plasma membrane shape. We previously found heterogeneity in CCV formation, some vesicles form with simultaneous membrane bending and clathrin assembly (constant curvature) and while others form with membrane bending following the accumulation of flat clathrin lattices (flat-to-curved).

Proteome maintenance is underpinned by molecular motors from the AAA+ superfamily. E. coli ClpA is a representative AAA+ motor that associates with the tetradecameric serine protease ClpP forming the ATP-dependent protease, ClpAP. ClpA, unfolds substrates targeted for degradation and translocates them into the central channel of ClpP where the substrate is degraded. However, when ClpA is not associated with ClpP, the motor uses its unfolding activity to noncovalently remodel protein substrates. Although a large body of work exists on the mechanisms of ClpAP-catalyzed protein unfolding and degradation, much less is known about the mechanisms of protein remodeling reactions.

Conserved NF-κB signaling pathways shape immune responses in animals. In mammals, NF-κB activation patterns and downstream transcription vary with stimulus, cell type, and stochastic differences among identically treated cells. Whether animals without adaptive immunity exhibit similar heterogeneity or rely on distinct immune strategies remains unknown. We engineered Drosophila melanogaster S2∗ live reporter cells as an immune-responsive model to monitor the dynamics of an NF-κB transcription factor, Relish, and downstream transcription in single cells.

Single-molecule analysis of guest-host peptide translocations via anthrax toxin protective antigen (PA) nanopores reveals a multi-state kinetic mechanism. K-Means clustering identified four distinct conductance states for all peptides tested, including a fully blocked state (State 0), two intermediates (States 1 and 2), and a fully open pore (State 3). Multi-exponential kinetic analysis of state-to-state transitions was performed, and the resulting lifetimes and amplitudes were correlated with molecular properties of the guest residue.