Protein Structure and Dynamics

Deep learning based design of buried hydrogen bond networks with HBDesigner

This paper introduces HBDesigner, a deep learning tool for designing hydrogen-bond networks in proteins, showing improved performance over existing methods.

Defining redundancy in the stickers and spacers of the cell-cell junction protein Canoe's intrinsically disordered region

The paper investigates the functional redundancy of stickers and spacers in the intrinsically disordered region of Canoe, revealing their roles in AJ function and robustness.

Native oligomerisation of a type I antifreeze peptide from winter flounder

This study examines the oligomerisation of AFP6, an antifreeze peptide from winter flounder, using structural prediction and biochemical assays, finding evidence for monomers, dimers, and larger oligomers.

cryoWEight: Conformational ensembles from cryo-EM particle images with weighted ensemble simulations

cryoWEight integrates cryo-EM data with weighted ensemble simulations to generate conformational ensembles of biomolecules.

Global analysis of thermal and chemical denaturation using CheMelt: Thermodynamic dissection of highly thermostable de novo designed proteins

The paper introduces CheMelt, a tool for analyzing thermal and chemical denaturation of proteins, and shows de novo designed proteins have lower thermodynamic parameters than natural proteins.

Scaffold-Constrained Generative Design Overcomes Failure Modes in Computational Protein Engineering

The paper develops a scaffold-constrained generative model for protein design, showing it produces high-quality candidates with better ranking scores than previous methods.

StrucNS reveals interaction-weighted network topology as the driving predictor of absolute stability of natural and de novo proteins

StrucNS predicts protein stability using network topology features, outperforming existing models and revealing key topological predictors of stability.

De novo design of flexible protein interactions with GuideFlip

GuideFlip co-designs protein structure and sequence for flexible targets, improving in silico success rates and experimentally validating binders to disordered proteins.

How informative are structural alphabets for representing protein folds?

This study evaluates how well three structural alphabets retain fold-level information compared to full-structure comparisons using TM-scores as a reference.

Probing the sequence variability tolerance in a de novo α-helical barrel biocatalyst

This study modifies de novo α-helical barrel biocatalysts using deep learning and computational methods to improve solubility and catalytic performance while maintaining structural stability.

Toward a Minimal Amino Acid Alphabet for Protein Design

The paper designs proteins using reduced amino acid alphabets and shows that 8 amino acids can form stable proteins, while smaller alphabets fail in experimental validation.

A directed TM->JM coupling in receptor tyrosine kinase dimers, set by activating mutations and the membrane environment

The paper uses MD simulations and computational methods to determine the direction of conformational coupling in RTK dimers, showing it correlates with receptor activity states.

Mechanism of molecular recognition revealed through dynamic drug binding pathways to SARS-CoV-2 main protease

This study reveals the molecular mechanism of nirmatrelvir binding to SARS-CoV-2 main protease using combined NMR titrations and weighted ensemble simulations, identifying two distinct binding pathways and key residues involved in resistance.

Unified modeling of mutation-induced protein stability responses with OmegaTherm

OmegaTherm predicts mutation-induced protein stability responses by jointly modeling folding free energy and melting temperature, achieving state-of-the-art performance in prediction and variant ranking.

MuseDrift: Navigating Protein Evolutionary Manifolds with Conditional Discrete Diffusion

MuseDrift generates protein variants with specified sequence identity to a wild-type sequence, achieving higher structural prediction confidence and better mutation-effect scores than existing methods.

The Apolipoprotein E N-Terminal Bundle Rendered Membrane-Compatible by Reverse-QTY Conversion Without Loss of Fold

This paper converts the N-terminal bundle of Apolipoprotein E to be membrane-compatible using reverse-QTY substitutions without altering its fold, demonstrating preserved helix content and increased hydrophobicity.

Extending the osmophobic effect to protein side chains with a physical transfer model across osmolyte classes

This study extends the osmophobic effect to protein side chains by developing a transfer model that accounts for backbone-side chain interactions, revealing different contributions of backbone and side chains to protein stabilization by various osmolytes.

Folding-Driven Control of the Functional PP1 Complex via Multiscale Modeling

The paper develops a multiscale model to study how conformational dynamics regulate the PP1-GADD34-eIF2 complex, showing folding-dependent assembly enhances biochemical function.

AtomWeaver: Multi-Component Flow Matching with a Structured Geometric Prior Facilitates Non-Canonical Peptide Design

AtomWeaver enables non-canonical peptide design by using a geometric prior to generate side-chain atoms without restricting residue identity, achieving high agreement with experimental results.

ProDive: detecting cross-family local conservation

ProDive detects cross-family local conservation using a pHMM-based framework, identifying 318,289 high confidence segment correspondences across 25,545 Pfam families.

AF3 Inspector: In-Browser 3D Model Visualization and Confidence Analytics for AlphaFold 3

AF3 Inspector provides an interactive web tool to visualize and analyze all AlphaFold 3 structural models, addressing limitations in the official service.

Targeted finetuning enables co-folding models to learn ligand-induced protein conformational states

The paper shows targeted finetuning can enable co-folding models to learn ligand-induced conformational states not present in training data.

Combining CHARMM36m with OPC water improves accuracy

This paper assesses the accuracy of different force field combinations for simulating intrinsically disordered proteins and finds that combining C36m with OPC water improves accuracy for IDPs without compromising globular protein simulations.

PolyA/polyQ-mediated conformational rewiring regulates DNA engagement and drives aggregation in the neuronal transcription factor Ascl1

This study shows that the polyA/polyQ tract in Ascl1 regulates DNA engagement and aggregation through conformational changes, affecting solubility and cellular abundance.

Product-stabilized filamentation by human glutamine synthetase allosterically tunes metabolic activity

This paper shows human glutamine synthetase forms filaments stabilized by glutamine, reducing catalytic specificity for ammonia and linking product concentration to enzyme function.

Quantifying (de)Mixing of Disordered Proteins in Molecular Dynamics Simulations

This paper introduces a domain decomposition method to quantify mixing in disordered protein simulations, showing physicochemical similarity promotes mixing and identifying factors influencing condensate formation.

In-Silico Thermodynamic and Structural Profiling of Bacterial SoxB Thiohydrolase: Evaluating the Substrate Accommodation of Circular Potassium Thiosulfate in Sulfur-Deficient Alkaline Soils

The paper uses computational methods to evaluate how SoxB thiohydrolase binds thiosulfate in soil bacteria, finding higher binding affinity and structural stability under alkaline conditions.

Light Martini water accelerates sampling in coarse-grained molecular dynamics simulations

This paper introduces light Martini water, a modified water model that accelerates sampling in coarse-grained MD simulations without compromising accuracy.

COCOA-Tree: Phylogenetic visualization and comparative analysis of coevolving residues

COCOA-Tree reanalyzes coevolution datasets to uncover evolutionary properties of coevolving residues and shows different metrics identify distinct groups.

Shedding light on Gaussia Luciferase conformational space using multi-conformation enhanced sampling simulation

This study uses enhanced sampling simulations to explore the conformational space of Gaussia luciferase, revealing structural dynamics and substrate-binding features not captured by existing methods.