surface plasmon resonance
Surface plasmon resonance (SPR) is a way to watch a molecule stick to a target and let go, in real time, without attaching any tag or label to it. Picture a sensor surface so sensitive that it feels the tiny extra weight whenever something binds to a protein anchored on it — and feels the weight lift again when that something leaves.
Physically, the target protein is immobilized on a thin gold-coated sensor chip, and a solution of the test compound flows over it. Binding changes the mass at the surface, which shifts the angle at which light is absorbed by electrons (plasmons) in the gold film. The instrument records this shift as a real-time trace: a rising signal as the compound binds (association) and a falling signal as it dissociates (dissociation).
Because it watches binding directly and over time, SPR yields not just whether and how tightly a compound binds (affinity), but how fast it binds and unbinds — the kinetics of association and dissociation, and the residence time. This makes it a workhorse for fragment screening and hit confirmation, where confirming a real, direct binding event and its kinetics matters more than a single activity number. Its limits are that immobilizing the protein can perturb it, and very weak or very nonspecific binders demand careful controls.
In a fragment campaign, SPR distinguishes a genuine binder with a clean, dose-dependent sensorgram from an aggregator whose noisy, non-saturating signal betrays an artifact.
A clean, dose-dependent SPR sensorgram confirms direct, real binding to the target.
SPR's special power is kinetics: two compounds with identical affinity can have very different on- and off-rates, and a long residence time (slow off-rate) often matters more for drug effect than equilibrium affinity alone.