Nuclear magnetic resonance is used to study the conformation of molecules and proteins in solution, making it possible to analyze, in their native conformation, contacts between inhibitors and therapeutic targets with a view towards optimization of their interactions. The NMR probes on the many instruments in our laboratory excite, among others, the nuclei of hydrogen-1, carbon-13 and nitrogen-15, enabling us to study the properties of protein isotopes and conduct observational competition studies with fluorine-19.

This technique is used to determine the three-dimensional molecular structure of proteins, alone or with an inhibitor. It reveals the molecular structure of drug-binding sites and enables scientists to suggest chemical modifications that may improve drug binding to the target. Our well-appointed laboratory houses a powerful Xray generator and a host of tools to facilitate high-throughput and automation of the process (preparation of and optimization of suitable crystal forms and crystal imaging). Boehringer Ingelheim crystallographers also benefit from privileged access to synchrotron sources.

Computational chemists perform a variety of calculations on molecules and proteins to predict their conformation and structure and how they may interact with each other. In addition to a wide range of sophisticated software, computational chemists also have available to them a cluster of computers comprising nearly 700 processors. This broad-based network allows for expanded and accelerated calculation capabilities—a terrific advantage in the virtual screening of millions of compounds!

This discipline is to chemistry what bioinformatics is to biology. Chemoinformatics analyzes and processes information from databases on chemical structures obtained by high-capacity and virtual screening. It makes comparisons between molecules and illustrates trends that visually are not easily discernible, opening the door to other research paths. Chemoinformatics, in conjunction with computational chemistry, is an invaluable, value-added tool in virtual screening.