protein design

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.

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.

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.

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.

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.

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.

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.

TransPepMS: A Tool to Verify Peptides Absent from Reference Proteomes

TransPepMS verifies peptides not in reference proteomes by resolving ambiguities in mass-spectrometry data to distinguish genuine non-canonical peptides from false positives.

Function-preserving CD8⁺ T Cell Immunogenicity minimization through protein design

The paper develops a computational framework to minimize CD8⁺ T cell immunogenicity in designed proteins while preserving function, using a de novo luciferase as a model.

Computational Design and Evaluation of De Novo Protein Minibinders Targeting Specific Sites of STAT3

The paper designs and evaluates de novo protein minibinders targeting specific STAT3 sites using AI and AlphaFold3, identifying high-confidence binders with novel sequences.

Structural and Energetic Determinants of Monobody Recognition of Oncogenic KRAS Variants

This study identifies structural and energetic determinants of monobody 12D4 recognition of KRAS variants using simulations and redesign, revealing key interactions and mutations for improved selectivity.

A Specific Ancestral Sequence Reconstruction of Flagellin Can Drive Motility in Salmonella enterica but not Escherichia coli

This study uses ancestral sequence reconstruction to generate flagellin sequences and tests their ability to restore motility in E. coli and S. Typhimurium, finding limited sequence tolerance and species-specific differences.

Building from the ground up: augmentation strategies to improve protein language model performance on protein sets

This study investigates augmentation strategies to improve protein language model performance by reducing dataset size and enhancing generalization through active learning and generative models.

Projected Gradient Descent for Hallucination-Based Protein Binder Design

This paper evaluates projected gradient descent (PGD) for hallucination-based protein binder design, finding it improves design efficiency and diversity compared to softmax-based methods.

Astrolabe: Programmable all-atom biomolecular design through cross-context coordination and structural intervention

Astrolabe is a programmable framework for biomolecular design that coordinates molecular contexts and structures, achieving high pass rates in binder benchmarks and enabling complex assembly designs.

Do protein representations encode variant function? Diagnosing residue-level protein attributions via embedding-space gradients

This paper evaluates residue-level attributions in protein language models using synthetic fitness landscapes and identifies interventions that improve attribution accuracy.

Reinforcement learning with evolutionary priors unlocks multi-site enzyme optimization from sparse experimental feedback

AlphaVariant uses reinforcement learning with evolutionary priors to optimize enzyme variants from sparse experimental data, achieving high activity improvements in multiple rounds of optimization.

A rapid, automation-friendly, cell-free and purification-free pipeline for binding and kinetic characterisation of de novo designed binders with high quality standardised per-design data

This paper presents a rapid, automation-friendly pipeline for characterizing de novo protein binders without cell culture or purification, achieving binding affinity and kinetics in three days.

Mechanism-guided Discovery of Fluoroacetate Dehalogenase (FAcD) Variants for Enzymatic PFAS Defluorination

The paper presents DeFluorX, a pipeline using Boltz-2 to identify FAcD variants for PFAS defluorination by analyzing geometric and energetic factors in enzyme-PFAS complexes.

Complex enzyme active site scaffolding by iteratively detuned catalytic guidance

CaGE alternates guided structure prediction with sequence redesign, fading guidance each cycle, so sequences recover complex catalytic sites unaided; designed nonheme-iron and PLP-dependent enzymes were active.

De novo design of metalloenzymes using Metal Mer

This paper introduces a computational pipeline for de novo metalloenzyme design using Metal Mer, achieving high selectivity and activity in catalytic reactions without directed evolution.

Generative design of functional disordered regions in a developmental transcription factor

The paper designs functional disordered regions in a transcription factor using biophysical principles to predict chromatin binding function.

De novo design of cysteine proteases

This study designs de novo cysteine proteases with high activity and structural novelty, achieving 19% success rate and up to 3 x 10^7 rate enhancement over background reactions.

Evidence-resolved benchmarks separate biological context recognition from direct-partner specificity in protein interaction models

The paper benchmarks protein interaction models to distinguish direct partners from non-binding or noncontacting proteins, showing that context recognition and direct specificity are separable capabilities.

Computational redesign of Chlamydomonas reinhardtii photosynthetic fructose-1,6-bisphosphatase from the Calvin-Benson-Bassham cycle improves both stability and catalytic capacities in vitro

The paper computationally redesigns Chlamydomonas reinhardtii FBPase to enhance stability and catalytic activity, revealing insights into redox regulation and tetrameric assembly.

Reciprocal effective conductance-based inference of protein-protein relationships delineates protein network hubs and macromolecular properties

The paper uses effective conductance to infer protein-protein relationships and identifies network hubs and macromolecular interactions using a new tool called CoBRAA.

Computational design of protein conformational landscapes for metamorphic behavior

This study designs metamorphic proteins that switch between multiple conformations and shows how mutations can shift their conformational equilibrium.

Activation of Disease-Associated Polycystin-1 Mutants by Binding of Stalk-derived Agonist Peptides

The paper investigates how specific stalk-derived peptides can reactivate signaling in disease-associated PC1 mutants and uses computational simulations to support these findings.

Benchmarking interface confidence as a selection criterion for computational nanobody design against survivin's BIR-domain groove

The paper benchmarks interface confidence as a selection criterion for computational nanobody design against survivin's BIR-domain groove and finds it is not correlated with epitope engagement.