Biophysical Assessment of Target Protein Quality in Structure‐Based Drug Discovery
leadXpro CEO Michael Hennig contributes a chapter about the progress of structure biology in drug discovery
Publications
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.
Towards high throughput GPCR crystallography: In Meso soaking of Adenosine A2A Receptor crystals
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)
X-ray Free Electron Laser: Opportunities for drug discovery
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.
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.
Structural biology: doors open at the European XFEL
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.
Biophysics in drug discovery: impact, challenges and opportunities
A review by CEO Michael Hennig that discusses challenges and opportunities for biophysical methods in drug discovery.