Publications associées à Pyridomycin bridges the NADH- and substratebinding pockets of the enoyl reductase InhA

Computational drug development for membrane protein targets

Henning Paul-Julius Stahlberg, Pierre Vogel, Shuguang Yuan, Dongchun Ni, Babatunde Edukpe Ekundayo

The application of computational biology in drug development for membrane protein targets has experienced a boost from recent developments in deep learning-driven structure prediction, increased speed and resolution of structure elucidation, machine learni ...

2024

Cyclic Peptides for Drug Development

Christian Heinis, Xinjian Ji, Alexander Lund Nielsen

Cyclic peptides are fascinating molecules abundantly found in nature and exploited as molecular format for drug development as well as other applications, ranging from research tools to food additives. Advances in peptide technologies made over many years ...

Wiley-VCH Verlag GmbH2024

From Sequence to Dynamics to Function: Computational Design of Allostery and Ligand Selectivity in G-Protein Coupled Receptors

Mahdi Hijazi

The phenomenon of allostery, a general property in proteins that has been heralded as "the second secret of life" remains elusive to our understanding and even more challenging to incorporate into protein design. One example of allosteric proteins with gre ...

EPFL2024

Artificial intelligence for natural product drug discovery

Philippe Schwaller, Albert Hofstetter, Michael Alexander Skinnider, Florian Huber

Developments in computational omics technologies have provided new means to access the hidden diversity of natural products, unearthing new potential for drug discovery. In parallel, artificial intelligence approaches such as machine learning have led to e ...

Nature Portfolio2023

Optimised three-dimensional in vitro retinoblastoma models tailored for drug discovery and clinical translatability

Irina Sinenko

Retinoblastoma, while relatively rare, stands as the most prevalent intraocular cancer. In Switzerland, the survival rate approaches 100%, but it drops to less than 50% in low-income countries. The current treatment options for retinoblastoma rely on a lim ...

EPFL2023

A multi-reservoir extruder for time-resolved serial protein crystallography and compound screening at X-ray free-electron lasers

Camila Bacellar Cases Da Silveira, Christoph Bostedt

Serial crystallography at X-ray free-electron lasers (XFELs) permits the determination of radiation-damage free static as well as time-resolved protein structures at room temperature. Efficient sample delivery is a key factor for such experiments. Here, we ...

Nature Portfolio2023

Effective Inhibition of TDP-43 Aggregation by Native State Stabilization

Hilal Lashuel, Lixin Yang, Yllza Jasiqi

Preventing the misfolding or aggregation of transactive response DNA binding protein with 43 kDa (TDP-43) is the most actively pursued disease-modifying strategy to treat amyotrophic lateral sclerosis and other neurodegenerative diseases. In this work, we ...

Wiley-VCH Verlag GmbH2024

De novo protein design by inversion of the AlphaFold structure prediction network

Bruno Emanuel Ferreira De Sousa Correia, Stéphane Rosset, Casper Alexander Goverde, Benedict Dieter Gregor Wolf, Hamed Khakzad

De novo protein design enhances our understanding of the principles that govern protein folding and interactions, and has the potential to revolutionize biotechnology through the engineering of novel protein functionalities. Despite recent progress in comp ...

2023

Repurposed drug combination via high-throughput screening and dual drug delivery system development for the treatment of retinoblastoma

Po-Jen Tseng

The goal of retinoblastoma (RB) treatment is to save the child's life, eyes and functional vision, with that order of priority. The management of RB is complex and involves strategically chosen methods of surgical enucleation, external beam radiotherapy, i ...

EPFL2022

New methods for structure determination and speciation by NMR crystallography

Martins Balodis

NMR crystallography has been around for half a century, but with the advent of NMR crystal structure determination protocols in the last decade it has shown perspectives that were not seen before. Amalgamation of NMR and crystal structure determination has ...

EPFL2022

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

Polyanionic Amphiphilic Dendritic Polyglycerols as Broad-Spectrum Viral Inhibitors with a Virucidal Mechanism

Francesco Stellacci, Valeria Cagno, Matteo Gasbarri

Heparin has been known to be a broad-spectrum inhibitor of viral infection for almost 70 years, and it has been used as a medication for almost 90 years due to its anticoagulant effect. This nontoxic biocompatible polymer efficiently binds to many types of ...

American Chemical Society2022

Combi-seq for multiplexed transcriptome-based profiling of drug combinations using deterministic barcoding in single-cell droplets

Ngoc Hien Du, Christoph Merten

Anti-cancer therapies often exhibit only short-term effects. Tumors typically develop drug resistance causing relapses that might be tackled with drug combinations. Identification of the right combination is challenging and would benefit from high-content, ...

Nature Research2022

NICEdrug.ch, a workflow for rational drug design and systems-level analysis of drug metabolism

Vassily Hatzimanikatis, Noushin Hadadi, Jasmin Maria Hafner, Anush Chiappino-Pepe, Homa Mohammadi Peyhani

The discovery of a drug requires over a decade of intensive research and financial investments – and still has a high risk of failure. To reduce this burden, we developed the NICEdrug.ch resource, which incorporates 250,000 bioactive molecules, and studied ...

2021

Can Precision Electrophile Signaling Make a Meaningful and Lasting Impression in Drug Design?

Yimon Aye, Amogh Kulkarni

For several years, drugs with reactive electrophilic appendages have been developed. These units typically confer prolonged residence time of the drugs on their protein targets, and may assist targeting shallow binding sites and/or improving the drug-prote ...

WILEY-V C H VERLAG GMBH2022

Methods for the generation of large combinatorial macrocycle libraries

Sevan Mleh Habeshian

Macrocycles are an attractive class of molecules due to their good binding properties and yet rather small size that allows, in many cases, crossing membranes to reach intracellular targets. In comparison to classical small molecule drugs, macrocycles are ...

EPFL2021

High-content, targeted RNA-seq screening in organoids for drug discovery in colorectal cancer

Jörg Hülsken, Paloma Ordonez Moran, Maxim Norkin

Organoids allow the recapitulation of intestinal homeostasis and cancerogenesis in vitro; however, RNA sequencing (RNA-seq)-based methods for drug screens are missing. We develop targeted organoid sequencing (TORNADO-seq), a high-throughput, high-content d ...

2021

Macrocycle synthesis strategy based on step-wise “adding and reacting” three components enables screening of large combinatorial libraries

Gerardo Turcatti, Jonathan Patrice Vesin, Christian Heinis, Alessandro Angelini, Alessandro Zorzi, Julien Bortoli Chapalay, Sangram Shivdas Kale, Kaycie Marie Butler, Ganesh Kumar Mothukuri, Carl Leonard Stenbratt

Macrocycles provide an attractive modality for drug development, but generating ligands for new targets is hampered by the limited availability of large macrocycle libraries. We have established a solution-phase macrocycle synthesis strategy in which three ...

2020

Structural investigation of InSe layered semiconductors

Helmuth Berger, Daniela Pacilè

During the last decade, III-VI layered semiconductors (GaSe, InSe, GaS, etc.) have emerged as potential candidates for various applications, such as FET and optoelectronic devices. The properties of this class of layered materials are strongly dependent on ...

2020

Enhancing the Signaling of GPCRs via Orthosteric Ions

Horst Vogel, Shuguang Yuan

G protein-coupled receptors play essential roles in cellular processes such as neuronal signaling, vision, olfaction, tasting, and metabolism. As GPCRs are the most important drug targets, understanding their interactions with ligands is of utmost importan ...

AMER CHEMICAL SOC2020