Assaying Proteins in Solution:
A workshop to focus on BIO-SAXS

New England Structural Biology Association (NESBA) presents a one day conference on Protein Misfolding and Rare Genetic Diseases: From Human Genetics to Drug Discovery

LaCava Center
Bentley University
Waltham, MA 
Monday, September 10, 2012 
9:30 am - 5:00 pm

NESBA will co-host a one day event focused on BIO-SAXS in the home laboratory, topics which will be discussed are practical tips for optimal sample preparation, best-practice data analyses, incorporation of protein X-ray diffraction and NMR data and future directions. Significant advances have been made in instrumentation and there will also be dedicated opportunities to meet with the major BIO-SAXS equipment designers and manufacturers.

INTRO FOR PEOPLE WHO KNOW WHAT SAXS IS:

In recent years techniques using Small Angle X-ray Scattering (SAXS) have seen a resurgence in the structural biology community. Advances in instrumentation and software have made SAXS experiments more accessible than ever. The technique allows researchers to explore structural characteristics of large macromolecular complexes and dynamic proteins that are recalcitrant to study with X-ray crystallography or NMR. Despite the wide adaptation of SAXS in the academic world, the use of the technique in a drug discovery pipeline has been slower to take hold. This is in spite of SAXS applications that can include stability studies for biologics, conformation change upon ligand binding, and studies of large complexes, which are potential drug targets. The purpose of this NESBA conference is to bring together the pharmaceutical structural biology community and leading players in SAXS techniques and instrumentation to discuss the technique on a fundamental level as well as its application to drug discovery efforts.

FOR PEOPLE WHO HAVE NEVER HEARD OF SAXS:

The techniques of protein crystallography and NMR have lead to tremendous advances in our understanding of protein structure and protein-ligand interactions. This knowledge has made major contributions to drug discover efforts. However, these techniques have limitations that prevent them from being applied to all systems of interest. A third field, Small Angle X-ray Scattering (SAXS) was first developed in the 1950's and is complementary to traditional structural biology techniques. SAXS experiments examine the structure of biological molecules in solution, much like NMR. However, much larger structures can be explored allowing for the study of large functional complexes. Dynamic systems can also be studied with SAXS, whereas these targets would not be amenable to protein crystallography.

Like protein crystallography, SAXS utilizes an intense, well collimated X-ray beam. However, unlike crystallography in which the X-ray beam is diffracted into discrete reflections, SAXS results in a continuous scattering pattern. This pattern is recorded by a detector and analyzed to reveal structural information about the molecule in solution. Whereas NMR and X-ray crystallography yield high resolution, atomic-level detail, SAXS data are extremely low resolution. Nevertheless, much information can be contained in this low-resolution data. Researchers can learn about the stability and dynamics of a molecule, monitor conformational changes upon ligand binding, and look at the molecular envelopes of large complexes. Some have even used these envelopes to "place" structures that have been solved separately by X-ray crystallography. In this sense, SAXS data can be seen as a "glue" that links the information gathered from multiple, disparate techniques.

Schedule:

This meeting was sponsored by the BIO-SAXS equipment manufacturers and NESBA sponsors and, as such, there was be NO FEE for attendees.

Meeting Sponsors:

• Anton Paar
• Art Robbins Instruments
• Bruker
• Novartis
• Pfizer
• Rigaku
• Vertex

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