Biophysics and Structural Biology

Biophysics

• Suite of in-house biophysical techniques used to validate hits and progress towards elaborated molecules
  • NMR, SPR, ITC, MST, TSA, and ASMS
• Identification of site (orthosteric, allosteric, cryptic) and stoichiometry of binding
• Quantification of binding affinity (K_D, ∆S, ∆H, ∆G) and binding kinetics (k_on, k_off, k_inact)
  • Data invaluable in decision making process for future chemistry design cycles
• Elaboration of fragment hits to lead-like molecules using off-rate libraries (ORL) and crude reaction mixtures (CRM) by SPR, ITC, ASMS, and X-ray crystallography
• Ternary complex formation for PROTAC™ studies using SPR

X-ray Crystallography

Macromolecular crystallography:

• Over 7000 crystal structures determined for more than 70 targets
• Comprehensive crystallography construct design, including chimeras and surrogate proteins
• Multiple high-throughput crystallisation screening protocols using both commercial and in-house screens
• Optimisation of multiple crystal forms for high-resolution crystal structure determination
• Ligand-bound structure determination using both co-crystallisation and ligand soaking experiments
  • Fragment and mini-fragment crystal soaking experiments
• In-house X-ray source and access to multiple synchrotrons for continuous data collection
• Full refinement of all structures determined
• Comprehensive analysis and reporting

Small molecule crystallography

• Crystallisation method development and salt screening
• Structure determination using in-house X-ray source