Speaker: Robin Curtis, University of Manchester, UK

The Antibodies in Solution: a LINXS – NIST Webinar Series provides background information related to the currently ongoing LINXS antibody research program. This is a concerted experimental and theoretical effort that aims to investigate the properties of monoclonal antibodies in solution, which comprise a major platform for potential drug candidates and are of high academic and pharmaceutical interest. An international consortium of researchers at academic institutions, research centers, NIST and Novartis has teamed up for this. Didactical lectures given by members of the consortium on different experimental and theoretical topics that are highly relevant for state-of-the-art antibody research as well as insights from pharmaceutical industry will be broadcasted. A central aspect of the webinar series will be to illustrate the full power of neutron and X-ray scattering science that can be achieved in combination with complementary experimental methods and different unifying simulation techniques.

Abstract:

The topic of the lecture is on measuring and understanding the molecular basis of protein-protein and protein-solvent interactions by static light scattering.  A brief introduction to the theory underpinning static light scattering is covered.  Then we discuss how measurements made as a function of solution conditions, salt concentration and pH, can be used to separate out electrostatic interactions from other short-ranged attractive forces between proteins and to elucidate the basis for specific ion effects.  Lesser known is that light scattering measurements can also be used for measuring protein-solvent interactions in terms of preferential interaction parameters. Results are presented for preferential interaction parameters in solutions with sodium chloride, arginine chloride, or chemical denaturants, urea or guanidinium chloride. 

We show for the first time how the preferential interaction parameter can be measured for the folded and the unfolded state at the same denaturant concentration and then compare protein-protein interactions for folded and unfolded proteins.  The talk is concluded with a few examples relating dilute solution measurements of protein-protein interactions with concentrated solution properties such as phase behaviour and viscosity.