Protein Structure
Carboxypeptidase A
Alpha Chymotrypsin
Ribonuclease A
Receptor Sites
Double-Helix B-DNA


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Before we begin, it is important to realize that water molecules are absolutely unique.7 With symmetrical structures they have positively-charged protons in hydrogen atoms on two corners and negatively-charged electron pairs on the other two corners. As polar entities, they attract each other like magnets to form coordinated clusters and align their charged centers to form “hydrogen bonds” which tie them together at a variety of angles and distances 7.8 The bonds are weak, involving about 2 kcal/mole of energy,8 but they continually tie water molecules together like a zipper.

Water molecules have symmetrical structures with positively and negative charges on their surfaces

This type of bonding is considered to be the reason why water has such high melting and boiling points relative to other liquids.7 For example, each water molecule in liquid water is dynamically bonded to three or four other water molecules in a tetrahedral fashion compared with methane, CH4, where the molecules are about the same size and mass but are held together by extremely weak gravitational forces.7,8

Water molecules and methane molecules are about the same size and weight but the boiling point of liquid water is much higher.

The difference in boiling points between liquid water and liquid methane is a spectacular 243 degrees C (470 degrees F). Again, this high boiling point of water is attributed to point-charge hydrogen-bonding.7,8 However, recent neutron irradiation studies at the Stanford Linear Accelerator Center provided evidence that, at any instant, the largest ordered structural unit in liquid water is a trimer with two water molecules hydrogen-bonded more rigidly to a central water molecule.9 Molecular orbital calculations back in the 70’s forecasted that the most stable structural unit in liquid water would be the trimer but it was not until recently that it was detected.10

Adobe Systems

However, the trimer is extremely unstable at temperatures above 0oC and lasts only about 10-12 seconds, a million millionth of a second.13 Since molecules in the trimer are hydrogen bonded together with about 4.5 kcal/mole more energy than the normal point-charge bond,8,12 as each trimer forms, about 9 kcal/mole of energy is lost and, as it decays, similar units of quantized energy are absorbed. This energy exchange in forming and degrading the trimer is significant because it is similar to the energy absorbed in hydrolysis of the terminal phosphate bond of ATP. Although no studies appear to have been performed with regard to the role trimers may play in the transfer of quantized units of energy in biochemical processes, it may be extremely important.

In the internal regions of proteins, individual water molecules are held in relatively fixed thermodynamically-stable positions by point-charge bonding but, even there, they have high energy and continue to vibrate and rotate.2 If liquid water is cooled, molecular motion decreases, point-charge distances between molecules decrease and density increases. At 4oC, density reaches a maximum and, as cooling continues down to 0oC, mean distances between molecules increase and density decreases.7,8


Ice exists in two spatial forms: a kinetically-produced unstable cubic form and a thermodynamically-stable, hexagonal form.

Although pseudo-forms of ice have been proposed as responsible for the expansion of water as it approaches 0oC, the ordered hexagonal forms present in ice cannot be present because pure liquid water in a clean glass container can be cooled to as much as 30oC below zero without crystallizing. If an hexagonal surface, like that in ice or iodine crystals is present, crystallization would occur immediately at 0oC.7 On the other hand, increased trimer-formation might well be responsible for this decrease in density because water molecules would be expected to dynamically hydrogen-bond out away from them in more extended ordered forms.

However, if water is cooled on down to -40oC, crystallization occurs immediately.21 But the crystalline form produced is not normal ice - it is “cubic ice” in which all of the molecules are frozen in linear elements, 2.75A between the water molecules.22Although cubic ice forms most rapidly, it is unstable and, if formed at 0oC, isomerizes immediately into normal “hexagonal ice” in which, as illustrated above, some of the molecules are not in linear elements and distances between water molecules are 2.75A to 2.84A.22 In chemical terms, cubic ice is the “kinetic” product of bond-formation while hexagonal ice is the “thermodynamically” more stable form at normal atmospheric pressures.23

Based on X-ray studies by Isaacs in 1999, hydrogen bonds within ice are not the same as the point-charge bonds in stable proteins, they are “covalent” with the electron orbital clouds of adjacent water molecules around a central proton - like those between carbon atoms.12 In cubic ice, the linear elements have temporal internal stability but lack external, interactive stability.22


X-ray diffraction from the surface of water shows the presence of covalently hydrogen-bonded trimers and tetramers.

Although trimer-formation has been difficult to detect in liquid water, X-ray diffraction from the surface of pure water at 25oC by Narten and Levy in the 70’s showed the presence of trimers, with a mean dimension of 4.5 Angstroms and linear tetramers at 6.8A (2.76A between water molecules) while most molecules are 2.90A apart, held together by polarity and point-charge bonds with the freedom to rotate and exchange from one hydrogen-bonded position to another.10 Peaks of the trimer and tetramer are extremely weak because only a limited number are present at any instant. Like the trimer which forms in bulk liquid water, surface trimers and tetramers last only about a million millionth of a second12 but, by forming on the surface, they most likely propagate the formation of additional linear elements and may contribute to the high surface tension of liquid water.7


Although, pure liquid water can be super-cooled well below 0oC without crystallizing, as mentioned above, contact with surfaces in which the atoms are in regular hexagonal arrangements, induces immediate crystallization.21 Once hexagonal covalent hydrogen bonding is produced in one layer, it must induce hexagonal order in adjacent layers.10 However, in a recent study, it was reported that a surface with water molecules in repetitive five-membered pentagonal rings did not initiate crystallization, instead, it prevented crystallization and exhibited antifreeze properties.29

However, if gasoline or oil are on the surface of water, super-cooling is impossible because liquid hydrocarbon molecules in contact with water assemble in the same hexagonal arrangement as water molecules in the surface of ice.16 As shown below, hydrocarbon molecules in contact with water can exchange positions but form coordinated assemblies and are restricted from rotating end-over-end. Periodically, they form hexagonal clusters with the hydrocarbon molecules about 5 angstroms apart, the same as every-other water molecule in ice - this draws adjacent water molecules into hexagonal-bonding relationships and induces covalent electron overlap around protons, just as in ice.12

Oil molecules assemble as linear elements with hexagonal symmetry on the surface of liquid water.

Again, molecular orbital calculations performed back in the 70’s, supported the view that as many as six water molecules might bond together on hydrocarbon surfaces at normal temperatures and form a type of hydration layering.17,4 However, recent studies suggest that these ordered hexagonal units last only about 10-12 seconds.13 As a water molecule is bound by covalent bonds into a linear element, it releases 8 to 10 kcal/mole of energy to adjacent water molecules but, as it moves back to higher-energy point-charge bonding, it absorbs similar units of quantized energy from the hydrocarbon molecules – it is surface water molecules which, by moving spontaneously from order toward disorder, absorb energy from hydrocarbons and moves them from random motion into coordinated layers.4,16

Since contact between hydrocarbons and water imposes order on both, they respond as expected based on the second law of thermodynamics - they spontaneously move away from each other to minimize contact and increase options of motion. Two simple experiments demonstrate this Second Law of Thermodynamics. If oil and water are mixed rapidly, small droplets form. However, if the mixture is permitted to stand, the droplets coalesce into a single layer - both liquids move spontaneously to minimize two-dimensional ordering contact.

Oil and water, when mixed rapidly, form a suspension of droplets but, on standing, spontaneously form a single linear interface.

If water is placed on a wax surface, it forms balls - once again, to minimize two-dimensional order at the liquid/liquid interface in favor of one-dimensional ordering at the interface with air.

Based on the second law of thermodynamics, equilibrium systems move spontaneously from order toward disorder. However, as mentioned above, in moving rapidly from order toward disorder, water molecules at the interface absorb quantized units of energy from more massive slower-moving contact molecules, like those in oil, and drive them toward order. Oil molecules are driven into linearized layers and hydrophobic non-hydrogen-bonding polypeptides are driven into anhydrous assemblies in proteins.4 Thus, it is covalent order in surface water which provides for spontaneous assembly within living cells and the movement from disorder toward order in biomolecular evolution.20

Support for this thesis was provided by Lumry and Rajender in 1970 who published a 102-page summary of energy changes which occur when proteins interact with small molecules in aqueous solution.15 They concluded that the processes involved an “Energy Compensation Phenomenon” – that there is a “linear relationship between enthalpy and entropy changes.” In other words: in aqueous solution, entropy and enthalpy changes in surface water as small molecules interact with polypeptides are balanced by equal and opposite changes within the polypeptide. Since polypeptide folding involves the same type of hydration-state interactions, most likely they involve the same type of Energy Compensation. As water moves from the covalently-hydrogen-bonded surface state to the liquid state, quantized units of energy are systematically removed from polypeptides to move them into lower internally-bonded energy states.


As you will see when we view the spatial structures of natural molecules, it is the distribution and nature of atoms on each surface which defines the degree and orientation of transient linear elements of hydration order on those surfaces. Just as the hydrocarbon molecules in oil spontaneously move away from contact with water in favor of associations with their own kind, water-ordering (hydrophobic) surfaces of specific lengths on polypeptides have evolved to assemble spontaneously and permit unstable covalently-ordered elements of water to leave. For example, the insulin molecule shown below is produced as a single linear strand of polypeptide which can exist in virtually an infinite number of conformations with an almost infinite number of modes of freedom.

The insulin molecule assembles together as A and B units to produce a protein with an anhydrous central core.

However, three sequences of peptides with hydrophobic hydrocarbon side chains rapidly induce the formation of adjacent covalent linear elements of hydration. Initially, those regions most likely are straightened by surface water, but then, the chain, by rotating through a number of transient hydrated forms, spontaneously forms three helical coils which dramatic decrease surface hydration. Residual complimentary elements of linear hydration on hydrophobic surfaces of the coils and residual linear segments then directs them into units A and B to bring lipid side chains together with small hydrating peptides like glycine and serine in critical positions in the polypeptide chain to permit turns and loops. Segment C is filled with small water-disordering glycine peptides to bring units A and B together to release residual ordered water from the middle of the molecule. Segment C and D, which is involved in transporting the insulin molecule through the cell membrane, are removed enzymatically to produce the final active hormone molecule.34

However, in contrast with most water-soluble proteins, the insulin molecule not only utilizes cubic hydration patterning to direct folding and assembly, it displays that patterning in its external structure.

The insulin molecule has a triangular shape to fit into receptor sites occupied by cubically-ordered water.

Since insulin is a hormone which binds to a receptor site in a membranal protein to initiate the transport of glucose into cells, it has a shape which reflects the cubic structure of water which it displaces from the open site. In fact, a recent study reported that it is the flat planar hydrophobic surface on the lower right-hand side (next to the coil and linear segment) which binds to the receptor site.35 Although no studies of hydration have been performed on that surface, Dr. Zewail and his group at CIT recently provided evidence, based on 4D ultra-fast crystallography, that water on solid planar electrophilic and hydrophobic surfaces is present in oriented layers with the patterning of cubic ice.25 Thus, if the lower right-hand surface of the insulin molecule could be examined, one would most likely find the same type of layering and cubic patterning. Although assemblies of proteins included in the chapters which follow are more complex, the basic principles of quantized surface-hydration are the same as those described above.

As polypeptides were produced at random during the early phases of molecule formation on earth, those with proper distributions of nonpolar, polar and ionic peptides spontaneously assembled to produce sets of molecules with unique functional properties. A molecular world evolved in which quantized transient elements of surface hydration guided molecular assembly and integrated function. It was a world in which the rules of spontaneity were reversed - random small molecules assembled, utilizing energy from the sun, to produce an almost infinite variety of more complex molecular forms. However, it was the symbiotic interaction of surfaces with water which defined which ones could assemble and function to produce the phenomenon we call “life” and which ones would be chewed up by the lytic properties of water.20


In the “Resting States” of nerve and muscle cells, when potassium ion levels are elevated internally and those of sodium and calcium depressed, water adjacent to inner surfaces adopts covalent dielectric linear configurations between surface ions which permit contractile proteins to relax and linearize.36 However, when sodium and calcium ions, which cluster water molecules around them37 rush into the cells, the order in surface water shifts from linear to circular, surfaces dehydrate, proteins shift conformations to conform with spherical hydration structuring and ATP-powered transport and contraction are activated.38

Sodium and calcium ions cluster water molecules around them in spherical forms to delocalize their charges.

Small cations like sodium, calcium and magnesium are called “order makers” because they increase the viscosity of water.7 By binding four to six water molecules around them in spherical configurations, they alter and increase the strength of hydrogen bonding in adjacent water molecules. Conversely, larger ions, like potassium and chloride, reduce the viscosity of water - they are called “order breakers. Since potassium ion is larger than sodium, it might be expected to bind water molecules more tightly but the positive charge on its nuclear core is so shielded by eight additional electrons that its positive charge is reduced to the point that it does not bind water molecules - it simply increases their rotational freedom as it passes.37

Potassium ions do not bind liquid water molecules, they simply alter rotational orientations as they pass.

Potassium ion spontaneously moves into water-ordering regions to increase local hydration entropy. On the other hand, sodium ions are excluded from linear water-ordering regions.7 As water linearizes to form ice, sodium ions are excluded while potassium ions are included. In fact, potassium ions increase proton-tunneling conductance of charge through ice.7,8 Even adjacent to double helix DNA, which has a high negative charge due to the abundance of surface phosphates, sodium ions are held out away from the surface by multiple layers of linearizing water molecules.28 By binding water molecules, a part of the positive charge of sodium ions is distributed out into those water molecules. However, the charge on sodium ions is so great that it passes outward toward oppositely-charged ions.

Protons pass through transient linear elements of hydration by charge-transfer tunneling to produce counter-ions adjacent to ions.

If oppositely-charged ions are far apart, rotation of water molecules between them is simply altered. However, charges often draw them close enough together that covalent dielectric hydrogen bonding is induced between water molecules and a proton on a water molecule adjacent to the sodium ion transfers, in cascade fashion through the quantized linear element, to form an hydronium ion next to the anion leaving a counter hydroxide ion next to the sodium. By binding water molecules around it and tunneling proton charge back and forth between the ions about 90% of the charge on a sodium ion is transferred to water.7,8,32

In pure liquid water, ion-formation is so low that it is an insulator, but sea water, like water within cells, it is a good conductor because it contains about 3% sodium chloride. If a low external voltage is applied to salt water, the current is carried primarily by the ions but, if the voltage is high enough, water molecules align between ions and pulses are transferred like lightning bolts by protons cascading through quantized, polarized quantized linear elements of water molecules from one ionic center to the next. In the axons of nerve fibers, this linear transfer of protonic charge along the inner surfaces of the membranes permits extremely rapid, almost superconductive, transfer of positive pulse.20,32,37

What is surprising is that the methods of energy storage and communication employed within living cells, which are extremely efficient, are not a part of present technology. For example, the inner surfaces of axon nerve fibers are composed of 1-to-1 complexes of lecithin and cholesterol which position anionic surface phosphates at precisely the separation of every-other water molecule in transient linear hydration.20 At the moment of nerve cell depolarization, with high charge differential between nerve endings and nodes, extended dielectric linearization of water permits protons to tunnel at extremely high speeds with essentially no movement of molecules or loss in energy.20,36 As pointed out on the Home Page, if our nerves were composed of metal, we would be combusted by the resistance. Technology today is searching for superconductivity – if nature had not already found it, we would not be here.


As mentioned above, by not hydrogen bonding with surfaces of fats and oils, water molecules are forced into more ordered quantized relationships.4 Conversely, polar atoms like oxygen and nitrogen, by hydrogen bonding with water molecules at a variety of angles and distances, form point-charge hydrogen bonds, disrupt linear covalent water-to-water hydrogen-bonding and increase mobility.30 Thus, outer surfaces of most water-soluble proteins contain numerous polar and ionic peptides which, by clustering water around them, disrupt coordinated linear hydration. By increasing the entropy of surface water, they permit surface groups on proteins to assume lower energy states and increase solubility.

On the other hand, there are regions on most water-soluble proteins which reinforce linear hydration order. It is those regions which bind complimentary ordering surfaces of other molecules, release ordered water from both surfaces and form reversible functional complexes.20 Often these ordering regions contain charged groups, like acids and amines, which induce the formation of quantized dielectric linear elements out from the surface in specific orientations to direct molecules with opposite charges into binding sites.26,32 As mentioned in the introduction, nuclear magnetic resonance of surface water on polysaccharides, proteins and nucleic acids produce the doublets of ice rather than the singlets of liquid water24 and similar studies suggest that water adopts preferred orientations on surfaces of collagen and muscle proteins.31

Although water molecules within and on surfaces of solid crystalline proteins are in thermodynamically stable positions, water on surfaces of proteins in solution are in dynamic motion, hydrogen-bonding with each other at a variety of angles and distances. Only intermittently, do covalent hydrogen-bonded linear elements form parallel with hydrophobic surfaces to provide for cubic patterning and structural order.17 Only intermittently, do quantized linear elements form between charged centers to permit proton tunneling and charge delocalization.26 Most of the time, surface water molecules are shifting from one point-charge hydrogen bonding relationship to another. Numerous recent studies support the view that water around large ions and adjacent to hydration-ordering surfaces is quantized with water molecules jumping from one quantized energy level to another – again, providing quantized order to motions and interactions in living cells.18 It is the order/disorder properties of water induced by surfaces of natural molecules which regulate their relative motions and interactions to provide for spontaneous and orderly function. It was the order/disorder property of surface water which selected them in the beginning as stable functional units and it is the same property which regulates their functions today.20


In spite of the fact that kinetically-produced linear elements which form on hydrophobic surfaces have half-lives that are short and not in equilibrium with neighboring molecules, they occupy space and would be expected to linearize hydrophobic surfaces and influence orientations of neighboring molecules. Furthermore, by forming as transient covalent linear elements between charged atoms and ions, they hold them at relatively quantized distances from each other to permit proton-mediated charge-tunneling to reduce charge potential.32 Although the increase and decrease in length of these linear hydrating elements might be considered to occur on the ends, recent infrared studies suggest they occur in the middle via a cyclic intermediate.13

The linear trimer may form by adding to the end of a dimer or to the middle through a cyclic trimer.

Thus, as charged atoms in proteins and nucleic acids move, single water molecules most likely move in and out of bridging linear elements to stabilize one hydration state to the next. As charged substrates and regulator molecules approach oppositely-charged binding sites, kinetically-produced linear elements decrease in length, probably one water molecule at a time,14 to direct them into the site.26 Each quantized linear element which forms, defines preferred stabilizing distances between ionic and polar atoms on surfaces.

In fact, numerous recent studies support the concept that water provides spatial quantization within living cells. As mentioned before, spectroscopic studies indicate the hydrogen-bonding between water molecules adjacent to surfaces and large ions occurs in quantized energy-exchanging steps from one bonding relationship to the next. Interfacial molecules move as Quantum Mechanical Entities - in discrete steps - not in smooth motions as anticipated by Newtonian Physics.18 Second: trimers revealed by high speed neutron bombardment, are believed to be formed from dimers in specific steps through the cyclic trimer.10 Third: in 2003, Professor Chatzidimitriou-Driesmann and his group in Germany reported that, when pure liquid water was bombarded with ultra-high-speed neutrons at 10-18 seconds, only 1.5 protons were scattered per water molecule rather 2.33  Since the protons in water molecules, like the electrons on metals, are subatomic entities, they exhibit both particle and wave properties. Just as the spin on electrons couples them together in “entanglement” waves at extended distances in wires, spins of protons tie water molecules together at extended distances as well.

Adobe Systems

Since these waves last only about 10-15 seconds, thousands of times shorter than the movement of molecules, a type of quantized proton ordering and energy exchange may be occurring at extended distances.19 In fact, as more information is gained regarding surface water in the brain it may be that consciousness and thought may involve integrated waves of proton entanglement. Thus, it appears that three types of quantized linear structuring exist in surface water: 1) water molecules are continually drawn into lines by tetrahedral hydrogen-bonding, 2) they form short linear covalent hydrogen-bonded elements that last about 10-12 seconds on hydrophobic surfaces and between charge centers and 3) they form quantized linear proton-coupled entanglement waves which last about 10-15 seconds.


Thus far, we have viewed the hydration order/disorder effects of hydrocarbons and ions on adjacent water but the alcohol groups on serine, threonine and tyrosine peptides play unique roles in the folding of polypeptides to produce proteins. Since ethyl alcohol, glycol and glycerin all depress the freezing point of water, it might be assumed that all alcoholic groups disrupt order in surface water. However, the effect of alcohols on hydration order and cubic patterning depends on the spatial relationship between the OH group on the molecule and surrounding water.

Cis-1,3,5-trihydroxycyclohexane, by fitting perfectly into cubic hydration patterning around it, serves as a seed for ice.

For example, the figure above illustrates how cyclohexane, as a hydrocarbon, tends to form a hydration cage around it. The cage shown has the unstable cubic structure but stable cages, with water molecules in pentagonal rings like bucky-balls, surround small molecules like methane.7 Adding three hydroxyls to the ring, as shown in the middle figure, might be expected to increase water solubility. However, the alcoholic oxygens fit perfectly into the cubic lattice of water around it - the compound is insoluble in water and seeds ice formation. On the other hand, the isomeric trans triol on the right, with one alcohol perpendicular to the ring, disrupts cubic hydration order - it is soluble in water, does not seed ice formation and depresses the freezing point of water.39

The glucose molecule does not hydrogen-bond strongly with water but transiently linearizes it on both its upper and lower surface.

Natural molecules, like glucose with six oxygens and five alcohols, are more complex. Some of its alcohols support transient linear hydration in one orientation but not in another. Detailed studies of hydration provide evidence that water does not bind strongly to glucose molecules.40 As you can see, the molecule is flat with oxygen atoms at positions 1 and 3 which can hydrogen bond with transiently-ordered trimers above the molecule and oxygens at positions 2 and 4 below. On the other hand, the angles of bonding with the central ring do not permit the alcohol groups to support linear elements of hydration in the plane of the ring. Thus, the glucose molecule, with its flat hydrocarbon-like upper and lower surfaces, exhibits “surfactant” properties: it spontaneously moves to hydration-ordering surfaces on membranes and proteins to displace covalently-ordered water and spontaneously move laterally in search of trimer binding sites in transport proteins where it can be transported into cells for combustion or conversion into essential molecules.

Glucose, C6H12O6, as the carbon and spatial analog of hexagonal water, H12O6, is one of the most abundant and important molecular forms on earth. But glucose is not alone: vital molecules like neurotransmitters and hormones have spatial structures which mimic ordered units of water and, as will be illustrated later, the central hydrocarbon, water-ordering regions of proteins tend to mimic the cubic-patterning properties of covalently-ordered water.

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