Fragment-based ligand discovery

Surface plasmon resonance (SPR). SPR directly measure the change in the mass of a molecule attached to a surface as it binds to a second molecule from solution. SPR can routinely measure K_D as weak as 5 mM. The method can be automated for relatively high throughput (hundreds of fragments per day), and can provide binding thermodynamics and kinetics. The challenge of the method is to fix molecules for assessment to the surface of a chip without interfering with possible interactions with molecules from the solvent. (See text for details.) The experiment shown here involves the titration of the compound Neu5Ac from solvent to a substrate-binding protein (SiaP) that had been covalently attached to the sensor surface.