Consilient mechanisms

Urry DW (2005) What sustains life Consilient mechanisms for protein-based machines and materials. Springer, Berlin Heidelberg New York... 

Urry, D.W. (2006) What Sustains Life Consilient Mechanisms for Protein-based Machines and Materials, Springer, New York, N.Y. 

The consilient mechanisms in relation to protein-based machines of biology are introduced. Before the four major assertions that... 

A diverse set of energy conversions that sustain life can be experimentally demonstrated by de novo design of elastic-contractile model proteins under the precept of a single, pervasive, mechanism, that is, by a consilient mechanism that creates a common groundwork of explanation. It is a mechanism that achieves function by controlling association of... 

By the Consilient Mechanism Protein-based Machines Require Water to Function... 

A protein-based machine without water as an integral part of its structure could not function by the consilient mechanism. In other words, water is required in at least one of the two states in order to have a movable cusp of insolubility, and in order for competition for hydration to be relevant there must be adequate water present. The first prerequisite, therefore, in addressing the biological relevance of the consilient mechanism is to assess whether or not water exists within or between the changing structural elements of a protein motor during function. 

Our special interest at this point is to gain insight into the presence and distribution of water within and around a motor domain, as would be required for the consilient mechanism to be relevant to motor function. Because it... 

Especially when seen in three dimensions, as in Figure 1.5 A, the stereo view of the myosin motor domain has the appearance of a sculpted surface. The surface contains crevices and depressions, as though formed from sandstone that had been weathered by wind and rain. Only a relatively few water molecules are seen in these surface recesses, because the majority of water molecules are too mobile to be observed by X-ray diffraction. Yet these surface crevices and depressions can be filled with water molecules that, by the consilient mechanism, contribute to the energy considerations of motor function. In this regard, it should be appreciated that only 10% to 20% of the existing water molecules are sufficiently fixed in space to be located by X-ray diffraction. ... 

When the space-filling protein component is removed, it becomes possible to view the located water molecules within the myosin motor. As shown in Figure 1.5B, an impressive number and distribution of the detected water molecules appear. It can also be expected that there are many more water molecules relevant to function of the myosin motor that are too mobile to be seen by X-ray diffraction, just as is apparent in the crevices and recesses of the surface. By the consilient mechanism these water molecules (seen in Fig. 1.5B and the additional unseen water molecules) are essential to motor function. These water molecules, which in our view are essential for Life, we choose to call the waters of Thales. Thus, as required for this protein motor to function by the consilient mechanism, internal water molecules do exist. Accordingly, in our view, this fundamental protein motor that produces motion contains ample water as part of the structure in order to function in the competition for water between oil-like and vinegar-like groups, which competition expresses as a repulsion between these groups. 

The energies interconverted by both of these steps are demonstrable by model proteins designed to function by the consilient mechanism of controlling phase separation. 

Considered Steps in the Fi-motor Synthesis of ATP as Shown by the Consilient Mechanism... 

B A space-filling view of all water molecules detected by X-ray diffraction demonstrates the internal waters of ITiales available to function by the consilient mechanism for protein-based machines. (Figure preparation was based on the crystallographic data of Abrahams et al. obtained from the Protein Data Bank, Structure File IBMF.)... 

Immediately below, we note the historical case of oxygen transport by hemoglobin from lungs to the tissues and note how this would be discussed in terms of the consilient mechanism. This was the first biological system appreciated for its positive cooperativity, the cooperative binding of oxygen molecules that is key to successful transport. 

The families of model proteins by which the fundamental mechanism is illustrated become designable materials with potential for sustaining both individual health and an increasingly complex and populous society. This includes all polymers operating under the consilient mechanism where adequate control over composition and sequence exists. 

It may be noted that present calculations of protein structure and function neglect the presence of so much internal water. In calculations, a quantity called the dielectric constant, required in electrostatic calculations of the energy of interaction between charges, is utilized. The value of the dielectric constant of bulk water is about 80, and commonly the assumption is made that the value shifts at the surface of the protein from 80 to 5 or less within the protein. The presence of the waters of Thales raises concern about such assumptions. Similarly, in Chapter 5, particularly in Figure 5.30, the experimental values could only be approximated by electrostatic calculations when a value of 5 or less was used, whereas direct measurement of the dielectric constant for the model protein system required that the value within the model protein motor be no less than 65. These points provide substantial support for the consilient mechanism. 

The correlations of Figure 2.6 represent one profound expression of the consilient mechanism for protein function in energy conversion that is, the data of Figure 2.6 represent a common groundwork of explanation" for protein function. 

Quite the inverse occurs for water-dissolved protein of interest here that is, by the consilient mechanism, heating from below to above the folding transition increases the order of the model protein. Because heating increases protein order, the transition is called an inverse temperature transition. 

Here we describe the coupling of functions. A function involves any chemical entity that can exist in either of two states, and by the consilient mechanism the two states differently affect hydrophobic hydration to a significant extent. Two functions become coupled when the more polar state of each decreases hydrophobic hydration while the more hydrophobic state of each increases the potential for hydrophobic hydration. The two functions can be a chemical couple such as -COO /-COOH and a redox couple such as the interconvertible states of oxidized nicoti-namide/reduced nicotinamide. 

The Fo-motor presents a simplistic utilization of the consilient mechanism. The repulsion, between a vinegar-like carboxylate of a cleat of a wheel and the sea of oil of a cell membrane, becomes an attraction on protonation, and the wheel rotates one cleat into the oily membrane as a second cleat rotates into a sufficiently polar/aqueous position for a carboxyl to release its proton to the other side of the membrane. The direction of rotation of the wheel and importantly of the axle (the y-rotor) that extends from the wheel depends on the frequency with which protons enter and leave from each side of the membrane. This straightforward demonstration of the consilient mechanism will be considered in more detail in relation to Figures 8.26 through 8.30. 

In the extramembrane component the y-rotor forms the stem and core of an orangeshaped structure comprised of six sections, three a-subunits and three P-subunits, arranged as threefold symmetrical (aP) pairs, designated as (aP)3. The key element of the consilient mechanism applied to ATP synthase is that the y-rotor exhibits three faces of very different hydrophobicity. In our view, rotation of the y-rotor by the Fo-motor causes the very hydrophobic side of the rotor to be spatially opposed, through a water-filled cleft, to the catalytic site containing the most charged state. 

From the perspective of the consilient mechanism, the assembly of filaments as required for muscle contraction and the necessary movement of components within the cell involves hydrophobic association/dissociation between composite subunits. The actin thin filament of... 

In Chapter 8, more structural background and molecular details of contraction exhibited by the linear myosin II motor are considered after, in Chapter 5, the physical basis for the apolar (oil-like)-polar (vinegar-like) repulsive energy that controls hydrophobic association is experimentally and analytically developed. The crystal structures of the cross-bridge of scallop muscle provide remarkable examples of the consilient mechanism functioning in this protein-based machine ... 

We again draw comparison by quoting from Schrddinger s What is Life as published in 1944 What I wish to make clear in this last chapter is, in short, that from all that we have learnt about the structure of living matter, we must be prepared to find it working in a manner that cannot be reduced to the ordinary laws of physics. In the present volume, our foundation is, of course, the somewhat counterintuitive inverse temperature transition. It is by means of the inverse temperature transition that the energies essential to sustain Life can, in fact, be accessed. This efficient consilient mechanism, however, requires no new laws of physics. In fact, the seeds of this mechanism are found in a 1937 report of Butler,in which he analyzed the thermodynamic elements of the solubility of oil-like groups in water. 

In this chapter we briefly note the improbability of a protein comprised of 20 different amino acids in specified sequence. Then we step through the details whereby a protein of specified sequence comes into being, and, like the accountant, sum up the cost in terms of the biological energy currency, adenosine triphosphate (ATP), that is, in terms of the number of ATP molecules consumed in the production of a protein of unique sequence. Such an essentially ordinary exercise requires inclusion in this book in order to remove unnecessary mystery of protein production, to provide an example whereby molecular machines utilize energy to produce biological structure, and to place in perspective the ease with which new protein-based machines evolve when functioning by the consilient mechanism. 

Consilient Mechanisms for Diverse Protein-based Machines The Efficient Comprehensive Hydrophobic Effect... 

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