(712d) Protein-Polyelectrolyte Assembly: Influence on Structural Stability

Assemblies of proteins with other charged macromolecules find important applications as pharmaceutical formulations, biocatalysts, drug delivery vehicles, and cell-contacting biomaterials. Despite their prevalence, the influence of polyelectrolyte assembly on protein structure and function is not well understood. Indeed, the recent literature includes examples of enhanced protein stability with polyelectrolyte assembly, as well as examples of diminished stability. We report here on the conformational stability of short, beta hairpin forming model proteins, assembled with various charged polymers of biological origin (poly(amino acids) and polysaccharides), as measured using molecular dynamics simulation and circular dichroism experiment. We find the temperature dependent extent of beta hairpin structure to vary significantly with polymer hydrophobicity and hydrogen bonding ability, and seek to understand these findings within a simple statistical mechanical lattice model. These studies lend important insight into the design of optimal polymers for diverse protein assembly applications, as well as broader questions on biomolecular (un)folding under crowded or heterogeneous conditions.