Biacore instruments use state-of-the-art label-free, real-time detection platform using surface plasmon resonance (SPR) to study protein-protein, protein-DNA/RNA, or protein-small molecule interactions. Biacore Molecular Interactions Shared Resource (BMISR) of Lombardi Comprehensive Cancer Center at Georgetown University School of Medicine was founded in 2006 shortly after the purchase of a Biacore T100 instrument through a shared instrument grant. Based on the success of this resource in serving the Georgetown University, biomedical research community and Lombardi Cancer Center in particular, in 2012 Biacore T100 was upgraded to a Biacore T200 by institutional funds. The success of this shared resource is evidenced by 23 peer-reviewed publications at high impact journals and federal research grants to multiple users totaling over $9,500,000 direct cost. The usage of the instrument had reached a stage where additional resources are needed to maintain and support the needs of the federally funded research community. Based on our recent success in targeting undruggable proteins in cancer, multiple investigators are now aiming to do small molecule screening experiments using the SPR technology. Since our current Biacore T-200 is not a high throughput system, we are requesting funds to acquire a Biacore 4000, which is better optimized for small molecule screening studies, built on the same cutting edge Biacore platform. With the availability of a number of small molecule libraries, Biacore 4000 will greatly advance the efforts in identifying high quality lead candidates that interact with high-value protein targets. Recently we were able to assess the usefulness and impact of Biacore 4000 to ongoing, as well as future research efforts by having access to a demo instrument for 2 months. During this short period of time we were able to screen 3926 compounds against 2 different proteins and identify potential binders/inhibitors. With our current capability, it would have taken more than 6 moths to generate and analyze this amount of data. Having maximized our current capability and effectiveness with T-200 instrument, Biacore 4000 will allow us to expand our expertise and services into a very valuable and much needed area of high throughput screening for drug discovery and translational medicine. Furthermore BMISR is an active partner of the Mid-Atlantic Shared Resources Consortium that includes Georgetown University, Johns Hopkins University, University of Maryland, and University of Virginia. Therefore the Biacore 4000 will not only serve members of Georgetown University but it will also help investigators at 3 other universities in our region. Six projects from these institutions are also included in this application.