Publications by Patrick Daniel Barth

Functional dynamics of G protein-coupled receptors reveal new routes for drug discovery

G protein-coupled receptors (GPCRs) are the largest human membrane protein family that transduce extracellular signals into cellular responses. They are major pharmacological targets, with approximately 26% of marketed drugs targeting GPCRs, primarily at t ...

2025

Minimal shuttle vectors for Saccharomyces cerevisiae

Patrick Daniel Barth, Sahand Jamal Rahi

Sophisticated genetic engineering tasks such as protein domain grafting and multi-gene fusions are hampered by the lack of suitable vector backbones. In particular, many restriction sites are in the backbone outside the polylinker region (multiple cloning ...

Oxford University Press (OUP)2025

Computational design of highly signalling-active membrane receptors through solvent-mediated allosteric networks

Patrick Daniel Barth, Lucas Sebastian Powell-Rudden

Protein catalysis and allostery require the atomic-level orchestration and motion of residues and ligand, solvent and protein effector molecules. However, the ability to design protein activity through precise protein–solvent cooperative interactions has n ...

Springer Science and Business Media LLC2025

Antibodies expand the scope of angiotensin receptor pharmacology

Patrick Daniel Barth, Shuhao Zhang

G-protein-coupled receptors (GPCRs) are key regulators of human physiology and are the targets of many small-molecule research compounds and therapeutic drugs. While most of these ligands bind to their target GPCR with high affinity, selectivity is often l ...

2024

Novel Natural Ligand Chimeric Antigen Receptors (cars) Targeting Cd70 with a Redesigned Cd27 Binding Interface Provide Enhanced Potency Against Acute Myeloid Leukemia

Patrick Daniel Barth, Lucas Sebastian Powell-Rudden

2024

Designed Tumor Microenvironment Responsive Biosensors Enhance Chimeric Antigen Receptor T Cell Therapy for Cancer

Patrick Daniel Barth, Lucas Sebastian Powell-Rudden

Cambridge2023

Variants of the gain domain of adhesion g protein-coupled receptors

Louis Georges Baptiste Dumas, Matthieu François Marfoglia, Patrick Daniel Barth

The present invention relates to variants of the GAIN domain (G-protein-coupled receptor autoproteolysis-inducing domain) of an adhesion G protein-coupled receptor (ADGRG), such as a GAIN domain variant comprising or consisting of the amino acid sequence o ...

2023

Designed biosensors for enhanced t cell therapy

Patrick Daniel Barth, Lucas Sebastian Powell-Rudden

This disclosure describes a method for de novo bottom-up assembly and rational design of allosteric biosensors with programmable input-output behaviors that respond to soluble factors selectively enriched in tumors and trigger co-stimulation and cytokine s ...

2023

Computer-implemented design of peptide:receptor signaling complexes for enhanced chemotaxis

Patrick Daniel Barth, Robert Everett Jefferson

The present invention relates to a computer-implemented method for engineering the interaction between a protein and a cognate peptide that are capable of forming a molecular complex, wherein the method comprises (a) preparing in silico a library of test p ...

2023

Computational design of dynamic receptor—peptide signaling complexes applied to chemotaxis

Andreas Füglistaler, Aurélien Laurent Jean-Charles Oggier, Mahdi Hijazi, Patrick Daniel Barth, Robert Everett Jefferson, Ana Paola Rico Villarreal

Engineering protein biosensors that sensitively respond to specific biomolecules by triggering precise cellular responses is a major goal of diagnostics and synthetic cell biology. Previous biosensor designs have largely relied on binding structurally well ...

Nature Research2023

Deep learning approaches for conformational flexibility and switching properties in protein design

Mahdi Hijazi, Patrick Daniel Barth, Lucas Sebastian Powell-Rudden

Following the hugely successful application of deep learning methods to protein structure prediction, an increasing number of design methods seek to leverage generative models to design proteins with improved functionality over native proteins or novel str ...

2022

Computationally designed GPCR quaternary structures bias signaling pathway activation

Patrick Daniel Barth, Robert Everett Jefferson

Communication across membranes controls critical cellular processes and is achieved by receptors translating extracellular signals into selective cytoplasmic responses. While receptor tertiary structures can be readily characterized, receptor associations ...

Nature Research2022

Method for generating variants of a protein

Patrick Daniel Barth

The present relates to a method for generating variants of a protein based on a native protein regulated by allosteric pathway, the method comprising:- i) providing 3D structures of the native protein;- ii) identifying at least one pair of coupled alloster ...

2021

Computationally designed GPCR quaternary structures bias signaling pathway activation

Patrick Daniel Barth, Robert Everett Jefferson

WILEY2021

Method for generating variants of a protein

Patrick Daniel Barth

The present relates to a method for generating variants of a protein based on a native protein regulated by allosteric pathway, the method comprising: - i) providing 3D structures of the native protein; - ii) identifying at least one pair of coupled allost ...

2021

Computational design of G Protein-Coupled Receptor allosteric signal transductions

Patrick Daniel Barth, Dániel Kéri

Membrane receptors sense and transduce extracellular stimuli into intracellular signaling responses but the molecular underpinnings remain poorly understood. We report a computational approach for designing protein allosteric signaling functions. By combin ...

2020

Structure of a D2 dopamine receptor-G-protein complex in a lipid membrane

Mahdi Hijazi, Patrick Daniel Barth

The D2 dopamine receptor (DRD2) is a therapeutic target for Parkinson's disease(1)and antipsychotic drugs(2). DRD2 is activated by the endogenous neurotransmitter dopamine and synthetic agonist drugs such as bromocriptine(3), leading to stimulation of G(i) ...

NATURE PUBLISHING GROUP2020

Macromolecular modeling and design in Rosetta: recent methods and frameworks

Bruno Emanuel Ferreira De Sousa Correia, Jaume Bonet Martinez, Thomas Huber, Lei Shi, Andreas Scheck, Patrick Daniel Barth, Hamed Khakzad, Alisa Khramushin

The Rosetta software for macromolecular modeling, docking and design is extensively used in laboratories worldwide. During two decades of development by a community of laboratories at more than 60 institutions, Rosetta has been continuously refactored and ...

NATURE PUBLISHING GROUP2020

An autism-linked missense mutation in SHANK3 reveals the modularity of Shank3 function

Li Wang, Patrick Daniel Barth, Wei Wang

2020

Computational design of orthogonal membrane receptor-effector switches for rewiring signaling pathways

Thamani Dahoun, Patrick Daniel Barth

2018