DMSE Doctoral Thesis Defense 

Computational Insights into Multivalently Binding Polymers

Emiko Zumbro

Thursday, July 2, 2020 

3:00 – 4:00 PM EDT 

Contact dmse-gradoffice@mit.edu for the guest link.

Multivalent binding occurs when multiple ligands on one species simultaneously bind to multiple receptors on another species. Multivalency is used throughout biology as a tool to enhance weak monovalent binding interactions, increase specificity of binding, and form conformal interfaces. Experimental studies have shown that synthetic multivalent polymers can successfully bind to viruses and toxic proteins with strong binding affinities, indicating that multivalent polymers are a promising tool for inhibiting pathogen attachment to and subsequent infection of cells. Multivalent polymers have also been revealed as essential components of membraneless organelles, liquid-like protein/nucleic acid droplets essential for healthy cell function. In this work, we use theory and simulations to provide an understanding of how the structure of multivalent polymers controls their binding affinity and function. We explore both dilute and concentrated target binding regimes where multiple targets bound to a polymer can create a cooperative effect that results in phase separation. We specifically investigate the effects of degree of polymerization, solvent quality, binding site heterogeneity, and backbone stiffness on binding affinity and the implications for the rational design of polymeric inhibitors and the formation of biocondensates. We hope our results will narrow the design space for optimizing the structure and effectiveness of multivalent inhibitors and provide insights on how multivalently binding polymers control phase separation in synthetic and biological systems.

Thesis Supervisors 

Alfredo Alexander-Katz, Associate Professor, Materials Science and Engineering, Massachusetts Institute of Technology

Thesis Committee 

Darrell Irvine, Professor, Materials Science and Engineering and Biological Engineering, Massachusetts Institute of Technology 

Katharina Ribbeck, Associate Professor, Biological Engineering, Massachusetts Institute of Technology

James Swan, Associate Professor, Chemical Engineering, Massachusetts Institute of Technology