Five Opportunities at the Interface Between Structural Biology and AI and their Impact on Drug Discovery
by Denis Bucher, Principal Scientist at leadXpro and Head of Molecular Modelling and Design
Listen to Michael Hennig’s talk at DDC 2022 about the impact of CGI and other biophysical methods on drug discovery for membrane proteins
Together with the Basel Biozentrum and the Institute of Medical Microbiology in Zurich, leadXpro solved the structure of the bacterial transporter LptDE to provide structural basis for the design of novel antibiotics.
leadXpro CEO Michael Hennig showcases examples of successful structure based drug discovery for challenging membrane targets
First Cryo-EM structure of the human TRPV4 ion-channel in the open conformation, in complex with an agonist.
In partnership with Bayer, leadXpro has generated protein and solved the cryo-EM structure of human TRPV4 in complex with the agonist 4α-PDD, providing novel information about agonist binding to this important drug target.
In a partnership with Boehringer Ingelheim, leadXpro generated protein and provided the X-ray structure data to advance their drug discovery programs on CCR2, a chemokine receptor target.
leadXpro, PSI, ETH and Sosei Heptares scientists present sensitivity improvements for XFEL measurements by using long wavelength pulses and improvements in data evaluation.
Small molecule AZD4635 inhibitor of A2AR signaling rescues immune cell function including CD103+ dendritic cells enhancing anti-tumor immunity
The publication provides evidence implicating suppression of adaptive and innate immunity by adenosine as a mechanism for immune evasion by tumors. Inhibition of adenosine signaling through selective small molecule inhibition of A R using AZD4635 restores T cell function
cross-presentation by CD103+ DCs resulting in antitumor immunity.
leadXpro AG announces its involvement in a multiparty research collaboration by delivering SARS-CoV-2 M-glycoprotein, a promising therapeutic target against Covid-19.
This crystallography review summarizes the current main strategies in sample delivery and their respective pros and cons, as well as some future direction.
One month after the groundbreaking ceremony of Park Innovaare’s new Innovation Campus, leadXpro is the first company to sign a tenancy agreement.
In situ crystallography as an emerging method for structure solution of membrane proteins: the case of CCR2A
The in meso in situ serial X-ray crystallization method enables structure determination of very fragile crystals.
leadXpro CEO Michael Hennig contributes a chapter about the progress of structure biology in drug discovery
Lundbeck partners with leadXpro to discover drugs for membrane protein targets by high-resolution X-ray and cryo-Electron Microscopy
Astex Pharmaceuticals partners with leadXpro to facilitate structure-based drug discovery for membrane protein targets by cryo-Electron Microscopy
Crystal Structure of CC Chemokine Receptor 2A in Complex with an Orthosteric Antagonist Provides Insights for the Design of Selective Antagonists
Two independent structures of CCR2A in complex with the orthosteric antagonist MK-0812 were solved, confirming the importance of residue E2917.39 for antagonist binding. Structural modeling of pyrimidine amide antagonists showed an interaction with the non-conserved H1213.33, leading to a significant selectivity over CCR5, suggesting strategies for highly selective CCR2 antagonist design.
leadXpro and Sanofi collaborate for cryo-EM structure project
leadXpro determined the first protein structure at the Swiss Free Electron Laser (SwissFEL) facilities.
leadXpro AG and the University of Zurich (UZH) collaborate to generate sybodies as molecular discovery tools, therapeutic lead compounds and diagnostic reagents against disease-relevant membrane protein targets.
leadXpro AG and InterAx Biotech AG, join forces to discover and optimize new drug lead molecules targeting G-protein coupled receptors.
The paper reports an efficient method to generate multiple co-structures of the A2A G protein-coupled receptor (GPCR) with small-molecules from a single preparation of a thermostabilised receptor crystallised in Lipidic Cubic Phase (LCP)
leadXpro AG scientists explore the utility of cutting-edge X-ray technologies for the discovery of new therapeutics.
Creoptix and leadXpro AG announce the selection of the Creoptix WAVE technology by leadXpro to strengthen its capabilities for drug discovery aimed at identifying and optimizing drug candidates directed against challenging membrane protein drug targets.
The authors demonstrate that XFEL structure determination has matured to reality and point out the many advantages of the technology: Unmet brilliance and focus, femtosecond pulses and low/no radiation damage and measurement at room temperature allow structure determinations of challenging systems like membrane proteins, investigation of time-resolved ligand binding, new structural insights due to room temperature and full automation of crystal diffraction experiments.
leadXpro and AXXAM announce the collaboration for the discovery of small molecular ligands to a novel inflammation related GPCR target.
Serial millisecond crystallography for routine room-temperature structure determination at synchrotrons
We demonstrate that serial millisecond crystallography at a synchrotron beamline equipped with high-viscosity injector and high frame-rate detector allows typical crystallographic experiments to be performed at room-temperature.
A technology feature by Nature Methods’ technology editor Vivien Marx about free electron lasers to comment on the opening of the European X-ray Free Electron Laser (EuXFEL) in Hamburg, Germany.
Tripling its physical footprint and with a new funding round secured, leadXpro AG is well-prepared for further development.
leadXpro AG announced today a collaboration with Bayer AG to enable structure based drug discovery of membrane protein targets, facilitated by single particle cryo-Electron Microscopy (cryo-EM)
Park InnovAARE files building application for leadXpro’s future home
leadXpro proudly reports a collaboration contract with Boehringer Ingelheim
Agreement with Paul Scherrer Institute on a beam line at the Swiss Light Source SLS
A review by CEO Michael Hennig that discusses challenges and opportunities for biophysical methods in drug discovery.
Heptares and leadXpro enter collaboration on powerful new approaches to GPCR structure determination for drug discovery