Neurofilament Light Chain under the Lens of Structural Mass Spectrometry.

Neurofilament light chain (NfL) is an early nonspecific biomarker in neurodegenerative diseases and traumatic brain injury, indicating axonal damage. This work describes the detailed structural characterization of a selected primary calibrator with the potential to be used in future reference measurement procedure (RMP) development for the accurate quantification of NfL. As a part of the described workflow, the sequence, higher-order structure as well as solvent accessibility, and hydrogen-bonding profile were assessed under three different conditions in KPBS, artificial cerebrospinal fluid, and artificial cerebrospinal fluid in the presence of human serum albumin.

Considerations in the search for epistasis.

Epistasis refers to changes in the effect on phenotype of a unit of genetic information, such as a single nucleotide polymorphism or a gene, dependent on the context of other genetic units. Such interactions are both biologically plausible and good candidates to explain observations which are not fully explained by an additive heritability model. However, the search for epistasis has so far largely failed to recover this missing heritability.

Odorant Binding Proteins Facilitate the Gas-Phase Uptake of Odorants Through the Nasal Mucus.

Mammalian odorant binding proteins (OBPs) have long been suggested to transport hydrophobic odorant molecules through the aqueous environment of the nasal mucus. While the function of OBPs as odorant transporters is supported by their hydrophobic beta-barrel structure, no rationale has been provided on why and how these proteins facilitate the uptake of odorants from the gas phase. Here, a multi-scale computational approach validated through available high-resolution spectroscopy experiments reveals that the conformational space explored by carvone inside the binding cavity of porcine OBP (pOBP) is much closer to the gas than the aqueous phase, and that pOBP effectively manages to transport odorants by lowering the free energy barrier of odorant uptake.

PatchProt: hydrophobic patch prediction using protein foundation models.

Motivation: Hydrophobic patches on protein surfaces play important functional roles in protein-protein and protein-ligand interactions. Large hydrophobic surfaces are also involved in the progression of aggregation diseases. Predicting exposed hydrophobic patches from a protein sequence has shown to be a difficult task.