Ligands often bind to proteins in multiple binding modes. Understanding ligand conformational heterogeneity in the binding pocket is important for modulating binding affinity and selectivity, and in turn for having better molecular recognition and function. For example, researchers used knowledge of the two distinct binding modes of mono-substituted ligands of the tyrosine kinase EphB4 to rationally design bi-substituted ligands with single conformation and higher affinity. In a different drug design project, nuclear magnetic resonance (NMR) spectroscopy identified minor population states of ligands binding to the antibiotic target LpxC, which hinted towards a larger cryptic binding site and led to the design of a larger and more potent antibiotic. Thus, improved understanding of binding mechanisms can be used to develop better inhibitors in structure-based drug design.