Physical Chemistry of Biological Free Energy Transduction As Demonstrated by Elastic Protein-Based Polymers

Abstract

This article, on protein-based polymers comprised of repeating peptide sequences, reviews studies from the author's laboratory covering a period of more than two decades; it presents a general mechanism for protein folding and function and demonstrates the mechanism by designing model proteins capable of performing many of the energy conversions that sustain life and by designing diverse biomolecular machines and materials with promising applications for society. All polymers with the correct balance of apolar and polar moieties, including water soluble proteins and protein-based polymers, increase order by a hydrophobic folding and assembly transition as the temperature is raised above a critical onset temperature, designated as Tt. Instead of varying the temperature, however, innumerable variables lower the value of Tt from above to below the operating temperature to drive folding and function. Thus, this inverse temperature transition provides a fundamental mechanism whereby proteins fold and function and whereby the energy conversions that sustain living organisms can occur at constant temperature. Phenomenologically, this mechanism results in five axioms or principles for protein function and protein engineering whereby designed protein-based polymers interconvert six free energies interconverted by living organisms. The six intensive variables for biological free energy transduction are mechanical force, temperature, chemical potential, electrochemical potential, pressure, and electromagnetic radiation. No matter how seemingly disparate, virtually every protein function can be classified in terms of a form, or forms, of free energy transduction. Mechanistically, the design, preparation, and characterization of families of related protein-based polymers show the usually considered electrostatic charge−charge interactions not to be the physical basis for the energy conversions. Instead, presented and analyzed experimental data indicate competition for hydration between apolar and polar species to be responsible. In short, the value of Tt is determined by the amount of water of hydrophobic hydration; hydration of polar species, as required on ionization, occurs at the expense of hydrophobic hydration and raises the value of Tt, and the energy required to destructure hydrophobic hydration results in hydrophobic-induced pKa shifts. Formalisms are outlined that describe hydrophobic-induced pKa shifts, related positive cooperativity of acid-based titration curves, and the involved energy conversions.