Sequence Effects on Thermodynamic Interactions in Protein Polymers

Biological polymers offer an as-yet unparalleled level of sequence control in polymer design, enabling them to achieve a wide variety of properties in natural systems. A key question is how tuning protein sequence changes coarse-grained interactions in protein-solvent and protein-protein systems. To explore this effect, we have studied the solubility of a wide variety of elastin-like proteins (ELPs) in cosolvent systems that include water, alcohols, and salts, providing tuning of the hydrophobicity and ionic strength of the solvent. We observe for the first time cononsolvency effects in ELPs, mapping in detail the phase diagram for one commonly studied sequence as a function of solvent conditions. To understand the effect of single residue mutations, we explored a variety of different hydrophobic, hydrophilic, and charged amino acid mutations within the ELPs, showing how the cononsolvency behavior changes as a function of sequence. Interestingly, proteins can have different phase behavior even if they are compositional isomers, showing that specific sequence effects can play a relatively large role in the thermodynamics of these systems in a way that remains poorly understood. Block copolymers are further explored to understand protein-protein interactions.