Elastic-contractile model proteins: Physical chemistry, protein function and drug design and delivery

Abstract

This review presents the structure and physico-chemical properties of ECMPs, elastic-contractile model proteins using sparse design modifications of elastic (GVGVP)(n); it describes the capacity of ECMP to perform the energy conversions that sustain living organisms; it arrives at the hydration thermodynamics of ECMP in terms of the change in Gibbs free energy of hydrophobic association, ΔG(HA), and the apolar-polar repulsive free energy of hydration, ΔG(ap); it applies ΔG(HA), ΔG(ap), and the nature of elasticity to describe the function of basic diverse proteins, namely - the F₁-motor of ATP synthase, Complex III of mitochondria, the KscA potassium-channel, and the molecular chaperonin, GroEL/ES; it applies ΔG(HA) and ΔG(ap) to describe the function of ABC exporter proteins that confer multi-drug resistance (MDR) on micro-organisms and human carcinomas and suggests drug modifications with which to overcome MDR. Using ECMP, means are demonstrated, for quantifying drug hydrophobicity with which to combat MDR and for preparing ECMP drug delivery nanoparticles, ECMPddnp, decorated with synthetic antigen-binding fragments, Fab1 and Fab2, with which to target specific up-regulated receptors, characteristic of human carcinoma cells, for binding and localized drug release.