Rapid advances in protein structure design have not translated to intrinsically disordered regions (IDRs). This is largely due to our incomplete understanding of how IDR sequence encodes function. Here, we use stem cell differentiation as a model to map functional sequence features in the IDR of transcription factor RU...
Lance T. Denes, Ryan J. Emenecker, Nongyun Wang et al.· bioRxiv (Cold Spring Harbor...· 0 citations
The elucidation of the atomistic structure of PrPSc has, disappointingly, not revealed the mechanism underlying prion propagation. This is because PrPSc has been shown to be a standard amyloid, and as such, it can only template a polypeptide chain that is unfolded. Therefore, while PrPSc can easily template the disorde...
Sanaz Sabzehei, Hasier Eraña, Iria Díaz-Arias et al.· bioRxiv (Cold Spring Harbor...· 0 citations
Rab GTPases are small GTP-binding proteins that play a central role in the regulation of vesicular traffic in all eukaryotes. Pluricellular eukaryotic organisms exhibit an increasing number of Rab GTPase-encoding genes, which may correlate with organismal complexity. However, the genome of the parasitic protist Entamoe...
Naurú Idalia Vargas-Maya, Jennifer Isabel López-Pérez, José A. Martínez-Álvarez et al.· Frontiers in Chemical Biolog...· 0 citations
Industrial biocatalysis relies on the cost effective production of active enzymes in heterologous hosts, yet a substantial fraction of candidate sequences fails during recombinant expression because sequence-level determinants of translational efficiency are not captured by conventional codon optimization alone. Here w...
Tanushree Jaitly, Nicholas R. Silvaggi, Harry R Horn et al.· bioRxiv (Cold Spring Harbor...· 0 citations
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By treating each of the 240 E8 root vectors as a phi‑scaled harmonic oscillator at the 132 Hz base frequency, we find that the 16 chord families correspond to resonant modes that drive directed protein folding pathways. The phi coupling induces a self‑similar scaling of the root vectors, producing a discrete set of 12...
Andrew Stewart Caldin· Zenodo (CERN European Organi...· 0 citations
Abstract Recognition of N6-methyl-adenosine (m6A) in the RNA sequences by the YT521-B homology domain-containing protein family paralogs 1–3 (YTHDF1–3) is a dominant layer of myriad cellular regulation. Dysregulated YTHDF paralog expression and activities have been reported in cancer, including glioblastoma multiforme...
Abstract Cell-penetrating peptides (CPPs) remain a leading nonviral strategy for the intracellular delivery of polynucleotides and folded proteins, but native α-peptide CPPs are constrained by proteolysis, dose-dependent cytotoxicity, and endosomal entrapment. Peptidomimetic redesign addresses these limitations by repl...
Protein misfolding diseases arise from topological phase transitions in the E8 fiber bundle where non-trivial holonomy around closed loops in configuration space creates wall crossings that trap proteins in pathological configurations. The 240 root vectors define "stability chambers" in fold space, and disease states o...
Andrew Stewart Caldin· Zenodo (CERN European Organi...· 0 citations
Mixed bacterial infections, including Gram-positive and Gram-negative pathogens, remain a major global health concern. Achieving efficient treatment of synergistic polymicrobial infections stills a tremendous clinical challenge due to antibiotic permeability barriers and resistance. Here, we construct a defect-engineer...
Path collective variables reduce a high-dimensional transition to a progress coordinate, s, and an orthogonal distance, z. Computing the free energy along s often requires restraining z, so that sampling embraces a tube centered on the reference path. However, a conventional fixed half-harmonic wall demands an a priori...
Radu A. Talmazan, Cheng Giuseppe Chen, Chenyu Tang et al.· The Journal of Chemical Phys...· 0 citations
Delay is an inherent feature of genetic regulatory networks. It represents the time required for the assembly of functional regulator proteins. The protein production process is complex, as it includes transcription, translocation, translation, folding, and oligomerization. Because these steps are noisy, the resulting...
Sean Campbell, Courtney C. White, Amanda M. Alexander et al.· SIAM Journal on Life Science...· 0 citations
Sequence differences between deposited macromolecular models and their UniProt references are recorded in the mmCIF category _struct_ref_seq_dif, and intentional substitutions are expected to populate _entity_poly.pdbx_mutation, the field that structured queries read. When a substitution is not declared, the difference...
Michael T. Varman· Zenodo (CERN European Organi...· 0 citations
A new machine-learning framework aims to improve the success rate of computational protein design while moving away from results that reproduce sequences found in nature.
