Protein-based machines model

Analogy Between Fully Charged Carboxylate (-COO ) State of Model Proteins and the ATP -bound State of Protein-based Machines... 

These results of 18 years ago, demonstrating the capacity of de wovo-designed model protein-based machines for the conversion of chemical energy into mechanical work, remain unex-... 

Figure 5.2. The four phase transitions of the model protein (GVGVP)2si in water over the temperature range from -20 to 120°C. The familiar transition of the melting of ice and the vaporization of water are shown with the relative magnitudes of the heats of these transitions to those of protein heat denaturation and to the innocuous looking inverse temperature transition near 30°C that we believe to be the basis of the function of protein-based machines of Life. See text for discussion.

Another example is the Principle of Le ChStelier, which may be stated as follows For any system at rest (at equilibrium) the introduction of a stress (in our case an input energy) causes the system to react in such a way as to relieve the stress (in our case by an output energy). This principle reasonably describes protein-catalyzed energy conversion, that is, the function of protein-based machines. Under prescribed conditions, properly designed model protein-based machines exhibit a behavior where for each action there is a reaction. In section 5.4, regardless of the action, which was any one of several different input energies, the performance of mechanical work was the reac-... 

When the transition zone is specifically the temperature interval, any change in oil-like character of the model protein-based machine moves... 

V in Table 5.5 with 0,2,3,4, and 5 F residues per 30-mer exhibits a systematic nonlinear increase in steepness, that is, in positive cooperativity, and an associated nonlinear increased pKa shift, as plotted in Figure 5.34. The energy required to convert from the COOH state to the COO" state systematically in a supralinear way becomes less and less, as more Phe residues replace Val residues. The energy required to convert from the hydrophobically dissociated state of COO" to the hydrophobically associated (contracted) state of COOH becomes less, as the model protein becomes more hydro-phobic. The elastic-contractile protein-based machine becomes more efficient as it becomes more hydrophobic. The cooperativity of Model Protein iv with a Hill coefficient of 2.6 is similar... 

The most efficient ojjerational design would be for the machine to operate over the range of the acid-base titration curve with the steepest An/Ap slope. Because the Hill coefficient, n, as defined in Equation (5.20) is a measure of the slope, it provides for ready comparison of efficiencies. The Hill coefficients for Model Proteins I through v are listed in Figure 5.34, and the slopes are plotted in the inset. Accordingly, the comparison of the efficiencies of Model Proteins i and v simply becomes iii/liy = 1.5/8.0 = 0.19. Thus, by increasing the hydropho-bicity by the replacement of five Val (V) residues by five Phe (F) residues, as indicated in Table 5.5, increases the efficiency of the protein-based machine by just over fivefold. 

As was discussed in Chapter 5, for Figure 5.17, addition of electrons to a positively charged redox group increases oil-like character and drives model protein folding, which result in contraction and the performance of mechanical work. The increase in affinity for electrons of the vitamin-like molecule that occurs on replacement of Val by Phe (see Figure 5.20C) makes for a more efficient electron-driven contraction. Thus, a genetic code that would allow easy mutational steps to become more oil-like would, here again, provide for evolution of more efficient protein-based machines. 

This chapter discusses key protein-based machines of biology to demonstrate the relevance of the hydrophobic and elastic consilient mechanisms. The objective in this chapter, therefore, is to investigate selected examples of biology s protein-based machines and to look at the molecular level for a coherence of phenomena with the designed elastic model... 

Qualitatively, the argument for using a low dielectric constant seems reasonable. The low dielectric constant comes into question, however, on closer scrutiny of experimental results on model proteins for which control of composition is possible, and it makes difficult what must be subjective judgments of a correct dielectric constant for water-filled clefts and crevices of various dimensions found in many protein-based machines. 

Even so, crystal structures provide the best snapshots of forces in action. Crystal structures provide an unparalleled opportunity to assess relevance to the major protein-based machines of biology of the free energy transduction so dominantly displayed by elastic-contractile model proteins (as developed in Chapter 5). If the apolar-polar repulsive free energy of hydration, AG.p, the operative component of the Gibbs free energy of hydrophobic association, AGha> is active in ATP synthase, then it should become apparent in these snapshots. 

The concept of two distinct but interlinked mechanical processes, expanded here as the coupling of hydrophobic and elastic consilient mechanisms, entered the public domain in the publication of Urry and Parker. Experimental results on elastic-contractile model proteins forged the concept, and the work of Urry and Parker extended the concept to contraction in biology. Unexpected in our examination of the relevance of this perspective to biology was to find the first clear demonstration of the concept in biology in a protein-based machine of the electron transport chain as a transmembrane protein of the inner mitochondrial membrane. Unimaginable was the occurrence of the coupled forces precisely at the nexus at which electron transfer couples to proton pumping. 

Such is our journey of Ionian Enchantment from de novo design of elastic-contractile model protein-based machines to enlightenment at a key juncture of energy conversion within living matter. 

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