Dr. Jeremy Schmit
Kansas State University
Many-body Protein Systems: Challenges of Timescale and Resolution
102 Cardwell Hall
Monday, January 27, 2014
4:30 p.m.
The properties distinguishing one protein from another are all determined by perturbations in the sequence of amino acid side chains. This complicates many problems in protein physics, like protein folding, because there is a wide range of relevant length scales. This problem is even worse with questions involving many-body protein interactions where the system sizes are much bigger and the timescale are often much longer. In this colloquium I will discuss two cases where we have used simple analytic models to reduce many-body protein systems to smaller problems that are tractable by modern computer hardware. First, pharmaceutical companies need to be able to predict the viscosity of antibody solutions in order to avoid wasting resources on molecules that will be too difficult to manufacture and deliver. We show that antibody solutions behave much like semi-dilute polymer solutions in that the viscosity is determined by molecular entanglements. These entanglements depend strongly on interactions between the antigen binding domains, which cause the antibodies to polymerize into longer structures. Secondly, there is a great need to understand the mechanism by which proteins self-assemble into disease-related aggregates called "amyloids." We show that the long timescale characterizing amyloid assembly is caused by the exhaustive sampling required to find the ordered structure of the final aggregate. By identifying the reaction coordinate characterizing this sampling process, we can use a series of small computer simulations to probe the effects of amino acid sequence on aggregation kinetics.
