The Structural Biology Core facility in the Department of Molecular Medicine is designed to support researchers in their drug discovery and structure-based drug design efforts. With the computing power of the USF Research Computing Central Instructional and Research Computing Environment (CIRCE) or Amazon Web Services (AWS), researchers can use DOCK 3.7 to virtually screen the ~ 1.5 billion compounds contained in the ZINC database to identify novel small molecule leads against their targets. Then, using the core’s Cytiva Biacore S200 Surface Plasmon Resonance (SPR) instrument or BioTek Cytation 5 plate reader, researchers can validate compounds identified and purchased from virtual screening. The Biacore S200 is Cytiva’s most sensitive SPR instrument, and specifically designed to characterize the interactions involved in LMW/fragment-based drug discovery. The core is also open to working with researchers to utilize their own assays for hit validation. From there, researchers have access to the core’s full array of protein crystallization equipment in order to capture a crystal structure of validated hits in complex with their targets.

This crystallization equipment includes:

1. Art Robbins Instruments Crystal Phoenix Liquid Handling Robot and the SPT Labtech Mosquito Xtal3, which allow researchers to quickly screen their protein of interest against an array of crystallization conditions and identify initial hits.
2. Formulatrix Rock Imager 1000 Crystal Imager, which serves as both an incubator for screening trays and as an imager. The Rock Imager can automatically image screening trays on set schedules, using visible, polarized, and UV light, and help to quickly identify new protein crystals.
3. Formulatrix Formulator 16, which can be used to aid in optimization of crystallization conditions, allows for the creation of novel crystallization screens that can be designed by researchers.

The core also possesses all the necessary equipment to enable researchers to freeze and ship crystals to national beamlines for data collection. As part of the Southeast Regional Collaborative Access Team (SER-CAT) at Argonne National Laboratory, the core has access to regular beamtimes at the Advanced Photon Source (APS), where crystal datasets can be collected in as little as three minutes. If required, the core can also aid in the solving and refinement of crystal structures.

As a USF core facility, the staff can provide user training, experimental design support, and sample preparation/analysis.

• Virtual screening/molecular modeling
• Protein purification
• Protein crystal screening/optimization
• X-ray data collection
• Solution/refinement of crystal structures
• Surface Plasmon Resonance (SPR)
• Hit validation