F. DiMaio

Towards high-resolution modeling of small molecule-ion channel interactions

This study evaluates two ligand docking methods for ion channel complexes, finding they can sample near-native poses but struggle to consistently identify them as top-scoring models.

An artificial intelligence accelerated virtual screening platform for drug discovery

The paper develops RosettaVS, an AI-accelerated virtual screening platform that identifies drug candidates with high binding affinity across two targets, achieving a 14% and 44% hit rate in under seven days.

Umbrella toxin particles produced by Streptomyces block mycelial growth of competing species

This study identifies umbrella toxin particles produced by Streptomyces that inhibit the growth of competing bacterial species, distinct from small molecule antibiotics.

Generalized Biomolecular Modeling and Design with RoseTTAFold All-Atom

This paper introduces RFAA and RFdiffusionAA, models that can predict and design complex biomolecular assemblies including proteins, nucleic acids, small molecules, and covalent modifications.

De novo design of highly selective miniprotein inhibitors of integrins αvβ6 and αvβ8

This paper designs highly selective miniprotein inhibitors for integrins αvβ6 and αvβ8 with picomolar affinity and therapeutic potential in a mouse fibrosis model.

Efficient and accurate prediction of protein structure using RoseTTAFold2

This paper introduces RoseTTAFold2, a protein structure prediction method that achieves AlphaFold2-level accuracy without using its key features, demonstrating the potential for diverse model architectures.

Cyclic peptide structure prediction and design using AlphaFold

This paper modifies AlphaFold to predict and design cyclic peptides, achieving high accuracy in structure prediction and de novo design with experimental validation.

Hallucinating protein assemblies

Deep network-based protein design generates symmetric homo-oligomers with high structural accuracy, demonstrating the potential for creating novel nanomachines and biomaterials.

Robust residue-level error detection in cryo-electron microscopy models

The paper develops MEDIC, a model to detect residue-level errors in cryo-EM structures, achieving 68% precision and 60% recall on validated structures and fixing multiple errors in rebuilt models.

Automatic and accurate ligand structure determination guided by cryo-electron microscopy maps

This paper develops a tool to automatically determine ligand structures from cryoEM maps and evaluates its accuracy across EMDB data.

Improving de novo Protein Binder Design with Deep Learning

This paper improves de novo protein binder design by using deep learning models to assess design success rates and computational efficiency.

Structural basis underlying specific biochemical activities of non-muscle tropomyosin isoforms

The paper determines cryo-EM structures of actin filaments with two non-muscle tropomyosin isoforms, revealing structural differences that explain their distinct functional roles.

AlphaFold accurately predicts distinct conformations based on oligomeric state of a de novo designed protein

The paper tests AlphaFold's ability to predict different protein conformations based on oligomeric state, finding it accurately predicts both monomeric and dimeric structures of a designed protein.

Cryo-EM Structures of CTP Synthase Filaments Reveal Mechanism of pH-Sensitive Assembly During Budding Yeast Starvation

The paper uses cryo-EM to study CTP synthase filament assembly in yeast, revealing pH-sensitive mechanisms and their role in starvation response.

Structure of the phosphoinositide 3-kinase p110γ-p101 complex reveals molecular mechanism of GPCR activation

The paper reports the cryo-EM structure of the p110γ-p101 complex, revealing how GPCR activation is mediated through interactions with Gβγ and identifying potential therapeutic targets.

Large-scale design and refinement of stable proteins using sequence-only models

The paper presents two neural network models for predicting and generating stable proteins based on amino acid sequences, showing improved stability in both expert-designed and model-generated proteins.

NONCANONICAL ELECTROMECHANICAL COUPLING MECHANISM OF AN HCN CHANNEL

The paper investigates the structural rearrangements in spHCN channels during activation and inactivation, revealing a noncanonical electromechanical coupling mechanism involving the A helix and cAMP binding.

Learning a force field from small-molecule crystal lattice predictions enables consistent sub-Angstrom protein-ligand docking

The paper improves protein-ligand docking by optimizing force field parameters using small-molecule crystal structures, achieving better binding structure prediction.

Outcomes of the 2019 EMDataResource model challenge: validation of cryo-EM models at near-atomic resolution

The paper evaluates cryo-EM model quality using benchmark maps, showing high accuracy and reproducibility across 13 teams and recommending multiple metrics for model assessment.

Structure and lipid dynamics in the A. baumannii maintenance of lipid asymmetry (MLA) inner membrane complex

This study reports cryo-EM structures of the A. baumannii MLA complex in different states and proposes a molecular mechanism for lipid transport.

Deep learning enables the atomic structure determination of the Fanconi Anemia core complex from cryoEM

This paper uses deep learning and computational methods to determine an almost-complete atomic model of the Fanconi Anemia core complex from a low-resolution cryoEM map.

Structural basis for autophagy inhibition by the human Rubicon-Rab7 complex

This study determines the crystal structure of the Rubicon RH domain bound to Rab7-GTP, revealing its mechanism of autophagy inhibition and validating it as a therapeutic target.

A generative algorithm for de novo design of proteins with diverse pocket structures

This paper introduces a generative algorithm for designing de novo proteins with diverse small molecule binding pockets, validated through experimental testing and showing improved stability and diversity compared to natural proteins.

Prediction of protein mutational free energy: benchmark and sampling improvements increase classification accuracy

The paper improves protein mutational free energy prediction by creating a balanced benchmark set and testing enhancements in the Rosetta software suite.

The cryo-EM structure of the bacterial flagellum cap complex suggests a molecular mechanism for filament elongation.

The paper reports the cryo-EM structure of the Campylobacter jejuni flagellum cap complex and proposes a model for filament-cap interaction.

Efficient consideration of coordinated water molecules improves computational protein-protein and protein-ligand docking

The paper introduces an improved energy model for protein-protein and protein-ligand docking that accounts for coordinated water molecules, enhancing native structure recovery.

Independent evolution of polymerization in the Actin ATPase clan regulates hexokinase activity

Yeast glucokinase activity is limited by its polymerization, which is critical for cell viability during glucose refeeding.

The HCN Channel Voltage Sensor Undergoes A Large Downward Motion During Hyperpolarization

This study measures the movement of the HCN channel's S4 helix during hyperpolarization using tmFRET and reveals a significant downward motion and tilting, providing insights into reverse gating mechanisms.

Structural basis for substrate gripping and translocation by the ClpB AAA+ disaggregase

The paper determines the cryo-EM structure of a hyperactive ClpB variant bound to casein and ATPγS to elucidate its substrate gripping and translocation mechanism.

Cryo-electron microscopy structure of the lipid droplet-formation protein seipin

The paper reports the cryo-EM structure of D. melanogaster seipin and proposes a model for its role in lipid droplet formation.