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Developmental biophysics, the application of physical concepts and methods to the investigation of developmental processes in biology, is a broad field covering all aspects of biophysics, from experiments to theory, from molecules to cells, tissues, and organisms, and across all kingdoms of life. However, this wide scope, which makes it fascinating, also renders it very challenging. The complex environment that covers multiple spatial and temporal scales places demands on measurements, and the interpretation of results can be difficult.

Nicotinic acetylcholine receptors (nAChRs) are critical ligand-gated ion channels in the human nervous system. They are targets for various neurotoxins produced by algae, plants, and animals. While many structures of nAChRs bound by neurotoxins have been published, the binding mechanism of toxins to the nAChRs remains unclear. In this work, we have performed extensive Gaussian accelerated molecular dynamics simulations on several Aplysia californica (AC) nAChRs in complex with α-conotoxins, strychnine, and pinnatoxins, as well as human nAChRs in complex with α-bungarotoxin and α-conotoxin to determine the binding and dissociation pathways of the toxins to the nAChRs and the associated effects.

Accurate estimation of the strength of the protein–ligand interaction is important in the field of drug discovery. The binding strength can be determined by using experimental binding affinity assays which are both time and labor consuming and costly. Predicting the binding affinity/energy in silico is an alternative approach, particularly for virtual screening of large datasets. In general, the distance-based terms such as electrostatic and van der Waals interactions are among the key determinants of binding energy.

Interfacial hydrogen bonding partly determines membrane structure, heterogeneity, and dynamics. Given the chemical diversity of lipids, it is important to understand how composition determines lipid-lipid interactions and how those are translated to H-bond populations and dynamics. Here we investigate the role of palmitoyl sphingomyelin (PSM) in modulating lipid H-bond networks in combination with dipalmitoyl phosphatidylcholine (DPPC) using of ultrafast two-dimensional infrared (2D IR) spectroscopy and molecular dynamics (MD) simulations.

(Biophysical Journal 124, 1–17; May 6, 2025)

(Biophysical Journal 122, 484–495; February 7, 2023)

Phosphatidylinositides (PIs), constitute only 1 to 3% of plasma membranes, but play vital roles in cellular signaling. In particular, phosphatidylinositol 4,5-bisphosphate (PIP2) is involved in processes such as cytoskeleton organization and ion channel regulation. Pleckstrin homology (PH) domains, are modular domains found in many proteins, and are known for their strong affinity for PIP2 headgroups. The role of lipid composition in PH domain binding to PIP2, particularly the inclusion of phosphatidylserine (PS), is not well understood.

Single molecule localization microscopy (SMLM) has revolutionized the understanding of cellular organization by reconstructing informative images with quantifiable spatial distributions of molecules far beyond the optical diffraction limit. Much effort has been devoted to optimizing localization accuracy. One such approach is the assessment of SMLM data quality in real-time, rather than after lengthy post-acquisition analysis, which nevertheless represents a computational challenge.We overcame this difficulty by implementing an innovative mathematical approach we designed to drastically reduce the computational analysis of particle localization.

SIGNIFICANCE: This study uncovers the molecular interactions between a GAPDH-derived antimicrobial peptide (AMP) and a fungal membrane model, revealing a novel antifungal mechanism. The findings highlight that specific leucine substitutions within the central α helix of the peptide play a key role in membrane thinning and ergosterol depletion, and enhanced membrane permeabilization in fungal membrane model. These insights provide promising directions for developing new antifungal agents with improved specificity and reduced toxicity, addressing the critical need for more effective therapeutic options against fungal infections.

The human genome consists of about 2 m of DNA packed inside the cell nucleus barely 10 μm in diameter. DNA is complexed with histones, forming chromatin fiber, which folds inside the nucleus into loops, TADs, A/B compartments and chromosome territories. This organization is knot-free and self-similar across length scales, leading to a hypothesis that the genome presents a fractal globule, which was corroborated by chromosome conformation capture experiments. In addition, many microscopy techniques have been used to obtain the fractal dimension of the genome’s spatial distribution from its images.