Design of Functional Protein Membranes*

Protein surfaces are composed of sub-nanometer domains, with different degrees of hydrophilicity. These domains play a crucial role in protein assembly, ligand recognition, and drug docking. We explored here the surface domains to disperse enzymes in organic solvents where their activity can be enhanced using random heteropolymers that mimic unstructured proteins in membraneless organelles. The analysis of the correlations between polar domains with the polar components of amphiphilic random heteropolymers mediated by water elucidates the formation of protein-polymer complexes with a core (protein)-shell(polymer) morphology that help stabilize the proteins’ structures and preserve their enzymatic activities in unfavorable solvents as observed in recent experiments (1). At a more coarse-grained resolution, we find that the proteins selectively favor the binding of random copolymers with similar monomer sequences (2). The balance between the energetic and entropy gains in polymer adsorption is determined by the spatial distribution of the polar and non-polar domains and the average composition of the polymers.

(1) B. Panganiban, et al. Science 359: 1239-1243 (2018)
(2) T. Nguyen, et al. PNAS 26, 6578-6583 (2018)