Harnessing the Strength of Structural Analysis to Reveal Hidden Binding Opportunities in Complex Targets
- Comparing apo versus ligand-bound structures across cryo-EM and crystallography datasets to detect induced-fit or cryptic pocket formation which enable alternate binding sites
- Addressing experimental challenges in resolving low-occupancy or transient pockets, including sample heterogeneity, preferred orientation, and conformational averaging in cryo-EM datasets
- Reviewing computational strategies for predicting and optimizing binding modes, and retrospectively benchmarking against internal structural data sets to drive confidence in predictive models