Inna Goreshnik

Accelerating protein design by scaling experimental characterization

This paper introduces scalable experimental and computational workflows to accelerate protein design by improving throughput, reducing costs, and enabling rapid validation of thousands of protein designs.

Protein design to broadly reprogram engineered T cell function

This paper designs proteins to reprogram T cell signaling pathways, improving CAR-T and TCR-T performance in solid tumor models.

Computational design of de novo integrated domains enables rational control of pathogen effector recognition in plant NLR immune receptors.

This paper designs de novo integrated domains using AI tools to enable plant NLR receptors to recognize non-cognate pathogen effectors, demonstrating functional immune responses and structural fidelity.

Integrin-independent Tie2 activation using de novo designed proteins

This paper designs a de novo Tie2 binder that activates the Angiopoietin-Tie2 pathway without integrin engagement, showing improved therapeutic potential in a mouse model of ARDS.

Generative design of sequence specific DNA binding proteins

This paper designs sequence-specific DNA binding proteins using deep learning, achieving a 100-fold improvement in success rates over previous methods.

Reprogramming CAR T-Cells with designed bioPROTACs

This paper demonstrates that bioPROTACs can reprogram CAR T-cells by targeting DNMT3A, offering a tunable alternative to gene editing for enhancing T-cell function.

Improved protein binder design using -pairing targeted RFdiffusion

Conditioning RFdiffusion on edge beta-strand pairing yields specific binders to polar targets, with in silico success above 9.2% versus 0.98% for hotspot-only conditioning.

Design of solubly expressed miniaturized SMART MHCs

This paper designs soluble, miniaturized MHC proteins that enable stable expression in E. coli and retain peptide and TCR binding specificity.

De novo design of high-affinity miniprotein binders targeting Francisella tularensis virulence factor

The paper designs high-affinity miniprotein binders targeting Flpp3, a virulence factor of Francisella tularensis, using physics-based and deep-learning methods, achieving sub-nanomolar affinities.

High-Throughput De Novo Protein Design Yields Novel Immunomodulatory Agonists

The paper designs novel cytokines by fusing computationally generated receptor-binding domains, identifying several that activate signaling pathways and have specific biological effects.

Computational design of pH-sensitive binders

This paper introduces computational methods to design pH-sensitive binders that dissociate under acidic conditions, demonstrating their application in targeting various receptors and proteins.

Computational design of sequence-specific DNA-binding proteins

This paper designs sequence-specific DNA-binding proteins computationally and validates them experimentally, achieving high specificity and affinity for target sequences.

Diffusing protein binders to intrinsically disordered proteins

The paper develops RFdiffusion to generate protein binders for IDPs/IDRs, achieving nanomolar affinity and functional applications in amylin and IL2RG.

Designed miniproteins potently inhibit and protect against MERS-CoV

This study designs miniproteins that inhibit MERS-CoV by targeting the spike protein, showing broad neutralization and protective efficacy in mice.

De novo design of miniprotein agonists and antagonists targeting G protein-coupled receptors

This paper presents computational methods for designing GPCR-binding miniproteins and validates them through high-throughput screening, producing agonists and antagonists for multiple GPCRs.

Massively parallel assessment of designed protein solution properties using mass spectrometry and peptide barcoding

The paper develops a method to assess solution properties of designed proteins using mass spectrometry and peptide barcoding, enabling analysis of large protein libraries.

Target-conditioned diffusion generates potent TNFR superfamily antagonists and agonists

This study uses target-conditioned diffusion to design high-affinity TNFR superfamily antagonists and agonists with switchable specificity.

Design of High Affinity Binders to Convex Protein Target Sites

This paper designs high-affinity proteins that bind to convex protein sites using geometrically matching concave scaffolds, achieving low nanomolar to picomolar affinities.

Designed Endocytosis-Triggering Proteins mediate Targeted Degradation and amplify signaling

The paper designs EndoTags to trigger endocytosis and degradation of target proteins, enabling tissue-specific targeting and therapeutic applications.

Multivalent designed proteins protect against SARS-CoV-2 variants of concern

The paper designs and characterizes trivalent miniprotein binders that neutralize SARS-CoV-2 variants with low pM IC50 values and provide prophylactic and therapeutic protection in mice.

Robust de novo design of protein binding proteins from target structural information alone

This paper designs small, stable proteins that bind to diverse target proteins using only structural information, achieving nanomolar to picomolar affinities.

De novo design of picomolar SARS-CoV-2 miniprotein inhibitors

The paper designs picomolar SARS-CoV-2 miniprotein inhibitors using computational methods and experimental validation, showing high potency and structural similarity to computational models.