protein structure

Affinity maturation of a single-domain antibody via rational mutagenesis informed by artificial intelligence

The paper uses AI-predicted protein structures to guide rational mutagenesis of a single-domain antibody, enhancing its binding affinity to IL-12 by eightfold.

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.

Intrinsically disordered regions influence protein motif usage in Drosophila Ubx and AbdA Hox proteins

The paper shows that intrinsically disordered regions in Drosophila Hox proteins affect the usage of conserved motifs near the homeodomain through context-dependent intramolecular interactions.

Modular Cell-Free Extract Mixing Enables Soluble, Active Biomanufacturing of Difficult-to-Express and Aggregation-Prone Proteins

The paper introduces a modular extract mixing strategy for cell-free protein synthesis to improve solubility and activity of difficult-to-express proteins.

Reduced emerin expression marks gastric cancer progression and invasive nuclear remodeling

This study shows reduced emerin expression correlates with gastric cancer progression and nuclear remodeling, similar to findings in breast cancer.

Scalable Decoupling Contact and Configuration Spaces in a Quantum-Enabled Protein Folding Workflow

This paper presents a hybrid quantum-classical framework for peptide folding, demonstrating a workflow that outperforms quantum refinement in structural accuracy for a short peptide.

Beyond Ramachandran distributions: quantifying secondary structure effects on amino acids and their pairs in the full torsional space

The paper extends Ramachandran diagrams by modeling amino acid and pair torsion-angle distributions conditioned on secondary structure elements, enabling more accurate conformational predictions.

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.

ALS-associated mutations reveal a conserved C-terminal self-assembly module in the TDP-43 low-complexity domain

The paper identifies the C-terminal conserved region (CCR) of TDP-43 as a self-assembly module, showing that ALS-associated mutations impair fibrillization and assembly kinetics.

Large scale prospective evaluation of co-folding across hundreds of Mac1-ligand complexes and three virtual screens

On 489 evaluable new Mac1 complexes, AlphaFold3, Chai-1 and Boltz-2 placed over half of ligands within 2 Å, but on docking hit-lists AF3 and Boltz-2 added little over docking.

Probing Physical Intuition in Large Language Models through Partner-Dependent Mutation Prediction

This study evaluates LLMs' ability to predict mutation effects based on structural data without using dedicated predictors, finding comparable accuracy to existing methods.

AlphaFold3 and Intrinsically Disordered Proteins: Reliable Monomer Prediction, Unpredictable Multimer Performance

AlphaFold3 pLDDT matches AlphaFold2 at calling disordered residues (Matthews correlation 0.693 vs 0.701); on disorder-containing complexes mean DockQ is similar, but interface features explain less variance (42% vs 58%).

Functional dynamics of the eukaryotic RNA exosome upon complex formation

The paper demonstrates functional dynamics in the eukaryotic RNA exosome using NMR and EPR, showing subunit flexibility and conformational changes in the Exo9 complex.

Human Metalloenzymes Are Disproportionately Linked to Disease: The HEAM Structural Annotation Resource

The paper introduces HEAM, a dataset of human metalloproteins annotated for metal-binding sites and catalytic function, showing metalloenzymes are enriched in disease-related variants and pathways.

Tensorizing Pairwise Structural Analysis: GPU-Accelerated RMSD and FCC Clustering in HADDOCK3 Without Structural Regression.

The paper accelerates structural analysis in HADDOCK3 by reformulating RMSD and FCC clustering as GPU-based linear algebra operations, achieving significant speedups without compromising accuracy.

Representing biological concepts as directions in foundation model embeddings

This paper shows that biological concepts can be represented as directions in foundation model embeddings, enabling interpretable and reusable analysis of diverse biological properties.

Filling the Missing Puzzle: Integrating Interaction and Evolutionary Information to Enhance Protein Fitness Prediction in Inverse Folding

This paper introduces zPolaron, a graph neural network for functional protein design that integrates structural, interaction, and evolutionary information, improving fitness prediction beyond structural compatibility.

Sequence context decodes multi-state conformational heterogeneity from crystallographic B-factors

This paper decodes multi-state conformational heterogeneity from crystallographic B-factors using sequence context, introducing BFC to improve accuracy and utility in structural biology.

A base-modifying enzyme extends the range of anti-phage defense provided by DNA glycosylases

Brig3, a DNA glycosylase from a soil metagenome, excises 5-hydroxymethylcytosine from T-even phage DNA; the glucose hydrolase BapA extends defense to glucosylated genomes such as wild-type T4.

PeTFlow: Flow-Matching Based All-Atom Peptide Design through Side-Chain State Tokenization

PeTFlow designs peptides by optimizing sequence, conformation, and side-chain packing using flow-matching and state tokenization, achieving high-quality results on benchmarks.

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.

Structural Basis of Human Kinetochore-Microtubule Coupling by the Ndc80 and Ska Complexes

Cryo-EM shows human Ndc80 and Ska complexes bound to adjacent microtubule protofilaments, linked by a SKA3 tether that passes Ska's preference for GTP-like lattice and tip tracking to Ndc80.

Buried Ion-Pairs Reshape Folding Pathways of Artificial Proteins

This study shows that buried ion-pairs in artificial proteins reshape folding pathways by introducing kinetic barriers that are overcome by hydrophobic collapse and core packing.

Chain-Length-Dependent Interactions of Polyethylene Nanoplastics with Human Catalase reveals Size based Nanoplastic Toxicity

This study investigates how different lengths of polyethylene nanoplastics interact with human catalase, showing that shorter chains are more likely to inhibit the enzyme.

De Novo Design of Flavoproteins with Controlled Excited State Dynamics

This paper designs de novo flavoproteins with controlled excited state dynamics using computational methods and experimental validation.

Ab initio CryoEM maps minimizing preferred orientation problems in heterogeneous mixtures: ReconSIREN

ReconSIREN is a deep learning framework that improves CryoEM map accuracy by addressing preferred orientation errors in heterogeneous samples.

FlexENN: A Graph Neural Network for Binding Energy Prediction of Globular and Intrinsically Disordered Proteins

The paper introduces FlexENN, a graph neural network that predicts binding energies for both folded and intrinsically disordered protein complexes, showing improved performance over rigid-body methods.

Predicted structure of the 89-kDa invasion-tip protein of Holospora obtusa, an endonuclear symbiont of Paramecium caudatum, suggests a pH-dependent conformational change

The paper predicts the structure of a 89-kDa invasion-tip protein from Holospora obtusa and suggests a pH-dependent conformational change may aid in escaping the host digestive vacuole.

Autofocusing molecular simulations for integrative structural biology of broad conformational ensembles

This paper introduces autofocusing, a method that improves molecular simulations by integrating experimental data, demonstrating its effectiveness for phospholipid bilayers.

Mechanistic Basis of Sulfo Transfer in a PAPS-Independent ArylSulfate SulfoTransferases Revealed by Crystallography and QM/MM Simulations

This paper elucidates the catalytic mechanism of a PAPS-independent ASST using crystallography and QM/MM simulations, revealing a two-histidine mechanism for sulfo transfer.