Abstract
Investigation of protein-ligand interactions is crucial during early drug-discovery processes. ATR-FTIR spectroscopy can detect label-free protein-ligand interactions with high spatiotemporal resolution. Here we immobilized, as an example, the heat shock protein HSP90 on an ATR crystal. This protein is an important molecular target for drugs against several diseases including cancer. With our novel approach we investigated a ligand-induced secondary structural change. Two specific binding modes of 19 drug-like compounds were analyzed. Different binding modes can lead to different efficacy and specificity of different drugs. In addition, the k(obs) values of ligand dissociation were obtained. The results were validated by X-ray crystallography for the structural change and by SPR experiments for the dissociation kinetics, but our method yields all data in a single and simple experiment.