protein design

Engineering Nanobody Conformational Switches

This paper engineers conformational switches using nanobodies that fold upon ligand binding, enabling customizable receptors and sensors for biomarkers and drugs.

Generative design of de novo AAV vectors with unique serological profiles

This paper designs de novo AAV vectors with unique serological profiles using a variational autoencoder, achieving transduction efficiency and nAb avoidance in human sera.

StableProt: Structure-Aware Deep Learning for Protein Thermostability (Tm) and Environmental Adaptation (OGT) Prediction

StableProt predicts protein thermostability and organismal optimal growth temperature using a structure-aware deep learning framework, achieving high accuracy and robustness across temperature regimes.

pLM-bVAE: protein language model-enhanced binary representation improves quantum annealing-based protein sequence design

This paper introduces pLM-bVAE, a binary variational autoencoder enhanced with protein language model representations, showing improved sequence reconstruction and design performance in quantum annealing-based protein sequence design.

PartiDesign: A structure-sequence co-design paradigm for practical all-to-all biomolecules design

PartiDesign is a structure-sequence co-design model that generates molecular structures and sequences for proteins, nucleic acids, and small molecules, achieving high design throughput across benchmarks.

AlphaFold 3 Prediction Accuracy and Reliability across RNA Structures and Protein-RNA Interfaces

This study evaluates AlphaFold 3's accuracy and reliability in predicting RNA structures and protein-RNA interfaces, finding that confidence scores do not always correlate with correct predictions.

Functional analysis of small-molecule and protein binding domains using monomeric streptavidin-based two-component biosensors

The paper develops a biosensor platform using monomeric streptavidin to evaluate binding domains for small molecules and proteins, demonstrating ligand-dependent activation with biotinylated targets.

Mapping and Probing the Substrate Scope of a Ketoamide-Forming Splicease by Computational Design

The paper uses computational methods to design and evaluate splicease variants for generating diverse ketoamide substrates, finding that top-scoring peptides are spliced more efficiently than single-point mutants.

Filament assembly confers the mechanical resilience of the IFI16 restrictosome

This study shows that IFI16 filament assembly provides mechanical stability to condensates by compacting DNA into ultra-stable tangles, contrasting with the sensitivity of HIN200-dsDNA complexes.

Target Specific Conformational Flexibility and Electrostatic Complementarity Modulate LTNF10 Peptide Binding to Phospholipase A2 Variants from Snake Venoms

This study investigates how charge and conformational changes in a peptide affect its binding to different snake venom PLA2 variants, revealing structural and electrostatic factors influencing affinity.

Conformation governs cellular behaviors of LRRK2 Parkinson's disease variants

This study identifies 'unlatching' as a common mechanism for Parkinson's disease-associated LRRK2 variants, showing increased membrane localization and decreased S935 phosphorylation.

Machine learning guided design of strong transcriptional activation domains

The paper designs functional transcriptional activation domains using machine learning and experimental validation, finding that over 90% of predicted sequences work in yeast.

De novo design of mini-proteins as specific binders to PACAP-38, a key mediator of migraine

This study designs mini-proteins that bind PACAP-38 with high affinity, showing improved potency and stability compared to earlier versions.

The Quagmire of Immunogenicity-Guided Antibody Design: Labels Limit Progress

The paper evaluates antibody design methods using immunogenicity labels and finds that format-based approaches outperform sequence-based predictors, but label inaccuracies limit progress.

AI-driven discovery and engineering of human endogenous nanocage proteins for mRNA delivery

The paper develops DeepDelivery, an AI platform that identifies human proteins for mRNA delivery, validating 80% of top candidates for efficient, non-inflammatory delivery.

Opposing Regulation of Tau Condensation by Phosphorylation Levels and Molecular Chaperone Interactions

This study investigates how phosphorylation levels and the molecular chaperone Bri2 BRICHOS opposingly regulate Tau condensation and aggregation, revealing their roles in tauopathies.

Intrinsic immune receptor triggering mechanism informs rational chimeric receptor design

The paper identifies CD3ε as a primary trigger subunit in TCR activation through phase separation with Lck, leading to the design of TRIG molecules that activate T and NK cells via endogenous receptor signaling.

EverGreen: A Calcium Sensing Fluorescent Protein with Ultra-Slow Response Properties

The paper introduces a fluorescent calcium biosensor with ultra-slow response kinetics, useful for applications where delayed signal detection is advantageous.

LPT: Orchestrating bounded agentic loops for automated protein binder design

LPT uses bounded agentic loops with LLMs and a curated database to design protein binders from natural language prompts, achieving high success rates with low computational costs.

Identification of PUFA interaction site on ASIC3 suggests a complex regulatory mechanism

The paper identifies a PUFA binding site on ASIC3 using MD simulations and electrophysiology, showing how DHA modulates channel gating and desensitization.

Efficient biological design via genomic in-context learning

This paper demonstrates that in-context learning in the genome language model Evo 2 enables efficient biological sequence design without additional training.

Strategies for Overcoming the Purification Challenges of Meis1 and HoxA9 and Their Functional Characterization

This study optimizes the purification of Meis1 and HoxA9 proteins and characterizes their DNA-binding and cooperative interactions.

Yra2 regulates proteolysis of Cse4 to prevent its mislocalization to non-centromeric regions for chromosomal stability in budding yeast

This paper identifies Yra2's role in ubiquitin-mediated proteolysis of Cse4 to prevent its mislocalization and maintain chromosomal stability in budding yeast.

Acetylation facilitates NPM1 anchoring in the nucleolus by boosting liquid-liquid phase separation

This study shows that acetylation of NPM1 at Lys27 and Lys54 promotes its anchoring in the nucleolus by enhancing liquid-liquid phase separation.

In situ loading of biologics on and tissue redirection of circulating extracellular vesicles with an anchoring nanobody

This paper demonstrates that NEV3, an EV-anchoring nanobody, enables in situ loading of proteins onto circulating extracellular vesicles and redirects them to specific tissues in vivo.

ATP-Free Fatty Aldehyde Biosynthesis Enables an Autonomous Lux-Based Bioluminescence System

The paper develops an ATP-free bioluminescence system using DOX to convert fatty acids to fatty aldehydes, enhancing stability under metabolic stress.

Discovering and designing multistate protein assemblies

This paper designs protein assemblies that switch between structural states using engineered interfaces, demonstrating temperature-responsive transitions from capsids to 2D arrays.

Cross-family learning transfers thermal adaptation between enzymes

This paper shows that thermal adaptation can be transferred between unrelated enzymes using a generative framework, improving thermostability without evolutionary homology.

Directed Evolution of Multimodal Plastic Degrading Enzymes

This paper demonstrates the directed evolution of a multimodal plastic-degrading enzyme capable of breaking down both polyesters and polyurethane.

Simulating protein evolution with programmable fitness objectives derived from modern protein models

This paper simulates protein evolution using programmable fitness objectives derived from modern protein models, showing that combined objectives improve evolutionary realism and molecular plausibility.