Urry D.W. (Ed.) What Sustains Life? : Consilient Mechanisms for Protein-Based Machines and Materials
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References
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Poly(GVGVP) stands for the repeating
sequence (glycyl-valyl-glycyl-valyl-prolyl)n,
also abbreviated as (Gly-Val-Gly-Val-Pro)n,
or even more simply as (GVGVP)n where n is
the number of times that the sequence of five
amino acid residues repeats. When given as
poly(GVGVP), the value of n is an unspecified
average but for our use below is quite large. For
the comparisons of interest here for develop-
ment of the Tt-based hydrophobicity scale, the
average value of n is of the order of 200.
70.
Comparisons of this type require a standard-
ized set of conditions of protein chain length, of
concentration of model protein, of solution
conditions, and of a chosen model protein
within which to make systematic replacements.
The chain length should approach 1,000 re-
sidues; the required concentration has been
determined to be 40 grams per liter or more;
the solution should have the same concentra-
tion of salt as occurs in biology, the so-called
physiological saline solution of 8.7 grams NaCl
in one liter; and the chosen model protein
should be elastic, should have an intermediate
temperature range for aggregation, should have
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A. Pattanaik, D.C. Gowda, and D.W. Urry,
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75.
Asima Pattanaik, private communication. The
value of the percentage phosphorylation of
Pattanaik et al.^"^ of 23.5% has been corrected
to 47% as an average of five runs. This gives a
ATt of 840°C (860°C-20°C).
76.
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216
5.
Consilient Mechanisms for Diverse Protein-based Machines
Inverse Temperature Transition of Some Elastin-
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Biopolymers, 31,465^75,1991.
77.
D.W. Urry, M.M. Long, R.D. Harris, and K.U.
Prasad, "Temperature Correlated Force and
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"Electromechanical Transduction: Reduction-
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a Model Protein to Perform Mechanical Work."
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Biochem. Biophys. Res. Commun.,lSS, 611-611,
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D.W. Urry, L.C. Hayes, D.C. Gowda, and T.M.
Parker, "Pressure Effect on Inverse Tempera-
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Chem.
Phys. Lett, 182,101-106,1991.
85.
L.A. Strzegowski, M.B. Martinez, D.C. Gowda,
D.W. Urry, and D.A. Tirrell, "Photomodulation
of the Inverse Temperature Transition of a
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Chem.
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86.
D.W. Urry, S.-Q. Peng, L. Hayes, J. Jaggard,
and R.D. Harris, "A New Mechanism of
Mechanochemical Coupling: Stretch-induced
Increase in Carboxyl pKa as a Diagnostic."
Biopolymers, 30, 215-218,1990.
87.
D.W. Urry and S.-Q. Peng, "Non-linear Mechan-
ical Force-induced pKa Shifts: ImpUcations for
Efficiency of Conversion to Chemical Energy."
/ Am. Chem. Soc, 111, 8478-8479,1995.
88.
R. Henze and D.W. Urry, "Dielectric Relaxation
Studies Demonstrate a Peptide Librational
Mode in the Polypentapeptide of Elastin." /.
Am.
Chem. Soc, 107,2991-2993,1985.
89.
R. Buchet, C.-H. Luan, K.U. Prasad, R.D.
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93.
D.W. Urry, S.-Q. Peng, and T.M. Parker, "Delin-
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Induced pKa Shifts in Polypentapeptides: The
Glutamic Acid Residue." /. Am. Chem. Soc,
115,7509-7510,1993.
94.
D.W. Urry, C.-H. Luan, R.D. Harris, and K.U.
Prasad, "Aqueous Interfacial Driving Forces in
the Folding and Assembly of Protein (Elastin)-
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D.W. Urry, S.-Q. Peng, D.C. Gowda, T.M.
Parker, and R.D. Harris, "Comparison of Elec-
trostatic- and Hydrophobic-induced pKa Shifts
in Polypentapeptides: The Lysine Residue."
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Design of Extraordinary Hydrophobicity-
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34,
889-896,1994, Figures 4 and 5B.
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D.W. Urry, D.T. McPherson, J. Xu, H. Daniell,
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The presence of positive cooperativity,
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dif-
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not properly described as random chain net-
works, as the adherents of the relevance of the
classical theory of rubber elasticity to protein
elasticity are compelled to argue.
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The change in chemical energy per mole
(AG/An), also called the change in chemical
potential (A|i), is proportional to the change in
pH required to go from the COOH state to the
COO"
state. Obviously for the narrower, steeper
curves a smaller change in chemical energy
would be required. The result would be a more
efficient energy conversion, if, for example, the
change resulted in the performance of mechani-
cal work, as treated below in section 5.9.5.
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C.-H. Luan, T. Parker, K.U Prasad, and D.W.
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Inverse Temperature Transition of Some
Elastin-based Polytetra-, Polypenta-, and Poly-
nonapeptides." Biopolymers, 31,465^75,1991.
118.
H. S. Harned and B. B. Owen, The Physical
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3^"^
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D.W. Urry, "What is Elastin; What is Not."
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D.W. Urry, K. Okamoto, R.D. Harris, C.F
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D. W. Urry, "Free Energy Transduction in
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D. W. Urry, "Five Axioms for the Functional
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lar Machines and Materials: Principle for
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(Peptide Science), 47, 167-178 (1998).
On the Evolution of Protein-based
Machines (Toward Complexity of
Structure and Diversity of Function)
"There is grandeur in this view of
Hfe,
with its several
powers, having been originally breathed into a few
forms or into one; and that... from so simple a
beginning endless forms most beautiful and most
wonderful have been, and are being, evolved."
Charles Darwin, 1859
On the Origin of the Species^
6.1 Introduction
This volume presents a consilient mechanism,
"a common groundwork of explanation," for
energy conversions whereby protein-based
machines interconvert the set of six ener-
gies interconverted by living organisms. This
chapter examines the simple stepwise process
whereby protein compositional changes can
access each of the six energy sources and can
improve the efficiency of each of a resulting 18
pairwise energy conversions.
How complex are the changes in model
protein composition required to obtain new
molecular machines capable of new energy
conversions? In fact, with knowledge of the
consilient mechanism, they are, by experimen-
tal demonstration, almost trivial! How com-
plex are the compositional changes required
to make a given molecular machine more effi-
cient? Again, by means of the rules emergent
from the fundamental mechanism, the requisite
compositional changes in the model proteins
are extraordinarily simple!
Given the common genetic code for all Life,
we now ask, how complex are the mutations
required to make the compositional changes
that access new energies and that make protein-
based machines more efficient? Remarkably,
arriving at the necessary mutations is uncom-
plicated! A single base mutation is all that is
required to access a new energy source or to
make a given energy conversion more efficient.
As we will discuss, by single base mutations, we
evolve a single molecular machine, a thermally
driven engine, step after naturally selected step
into diverse and increasingly efficient protein-
based machines capable of interconverting
the energies essential for Life. Interestingly,
the organization of the genetic code itself
delineates oil-like and vinegar-like residues
and allows evolution to be straightforward.
Accordingly, this chapter addresses the sim-
plicity of molecular evolution for biological
energy conversion. In presenting a scenario for
the evolution of protein machines, we accept
the challenge of Behe, which also underscores
the quintessential role of molecular machines
in Life's processes. In Behe's words, "if you
search the scientific literature on evolution,
and if you focus your search on the question of
how molecular machines—the basis of life—
developed, you find an eerie and complete
silence. The complexity of life's foundation
has paralyzed science's attempt to account for
it; molecular machines present an as-yet-
impenetrable barrier to Darwinism's universal
reach."^
Armed with the consilient mechanism for
energy conversion, the "as-yet-impenetrable
barrier" of Behe transforms into a springboard
218
6.2 Accessing Available Energies to Achieve Useful Function
219
for insight into early evolution of the molecu-
lar machines that sustain Life. Each step to
access an additional energy and each step to
achieve greater efficiency for a given energy
conversion represents a step toward greater
complexity of structure. Clearly, each such
single step underscores an improved capacity
to survive. If production of the molecular
machines of Life is such that each new and/or
more efficient naturally preferred machine is
achievable by a simple process, then, given the
Blueprint of Life seen in the genomes of
humans and lower species,^"^ there remains
Httle bewilderment in the natural flow toward
increased diversity and greater complexity.
Alvin Toffler, in his Forward for Prigogine
and Stengers' book Order out ofchaos,^ accepts
the message of Darwinian evolution with this
statement:
Imagine the problems introduced by Darwin and his
followers! For evolution, far from pointing toward
reduced organization and diversity, points in the
opposite direction. Evolution proceeds from simple
to complex, from "lower" to "higher" forms of Life,
from undifferentiated to differentiated structures.
And, from a human point of view, all is quite opti-
mistic. The (biological) universe gets "better" orga-
nized as it ages, continually advancing to a higher
level as time sweeps by.
For the universe as a whole, time's arrow
points to increasing disorder and uniformity,
yet for biology time's arrow points to increas-
ing diversity and complexity of structure and
function. We will see how this can be for the
structural evolution of the molecular machines
of Life. Then we examine how the molecular
machines, themselves functioning by the con-
silient mechanism, facihtate the creation of
order.
Life represents a perpetuating, diversifying
energy-collecting system of stepwise increasing
complexity. Is the physical mechanism for this
energy-driven march from disorder to order
itself efficient? As shown later in this chapter,
the answer here also becomes a simple yes.
Because of the way in which it accesses and
employs energy, Life represents an efficient
energy-driven assembling, ordering, negative
entropy machine.
The physical basis for this march toward
greater order with time is the special energy-
collecting, phase transition of biology, referred
to previously in this volume as an inverse
temperature transition. The separation of oil
from water and the repulsion of oil-like from
vinegar-like groups constrained to coexist along
a protein chain molecule, so readily positioned
by the genetic code for the biosynthesis of
protein, become the physical basis for biology's
energy-driven march away from disorder.
6.2 Accessing Available
Energies to Achieve
Useful Function
We recall the Szent-Gyorgyi assertion, "Motion
has always been looked upon as the index of
Life."^
Here, we begin with the historical
sequence of energy sources used in our
laboratory to produce motion by means of
elastic-contractile model proteins specifically
designed to be responsive to those differing
energy
sources.
Thermal energy (heat) and then
chemical energy in the form of increased
concentration of table salt (NaCl) and in the
form of increased concentration of acid were
considered in turn and found to cause elastic
strips,
made from properly designed model pro-
teins,
to contract and to produce motion. Also,
pressure energy produced motion by acting on
natural aromatic amino acids. The energy con-
versions were unmistakably demonstrated by
the simple visual observation of lifting weights,
that is, of pumping iron. This was not after-the-
fact rationalization of experimental results, but
rather successful designs of protein-based
machines intended to interconvert the energy
conversions subsequently demonstrated.
The preceding energy sources—thermal,
chemical, and pressure—acted directly on
the model proteins with natural amino acid
residues available through use of the genetic
code.
Accessing light and electrical energies
requires attachment of vitamin or vitamin-like
biological molecules to the elastic model pro-
teins after including yet another natural amino
acid. In all, five different input energies produce
220
6. On the Evolution of Protein-based Machines
motion, that is, result in the energy output
described as the performance of mechanical
work, which is easily observed as the lifting of
a weight. The following describes the simplicity
of changes in model proteins required to access
these energies to produce motion. In addition,
an appropriate pair of functional groups, by
being part of the same oil-Uke domain on phase
separation, can be utilized to interconvert any
two of the five different energy inputs that inde-
pendently produce motion.
6.2.1 Using Heat (Thermal Energy) to
Produce Motion
We begin, as the story for these protein-based
polymers began, by using temperature to drive
the phase separation mechanism as demon-
strated by a synthetic high polymer based on
a naturally occurring repeat of five residues.
Cross-linking the polymer composed of the
repeating pentamer, (GVGVP)25i, also given
below as Polymer I, produces elastic sheets or
strips (see Figure 5.14). Raising the tempera-
ture of the elastic-contractile sheet from room
temperature to body temperature, that is, to
above the temperature for the onset of the
phase separation, causes the oil-like groups
distributed along the extended protein chain
molecules that were surrounded by water to be
separated from water. As a result, the polymer
chains fold, producing a contractile event and
the lifting of a weight (see Figure 6.1).^"^
6.2.2 Using Salt (Chemical Energy) to
Produce Motion
With the same elastic sheets as above, addition
of salt (NaCl) lowers the temperature of the
phase separation from above to below the
operating temperature and drives contraction
with the moving of a weight, but without chang-
ing the temperature. A point to be made here is
the amount of salt required for achieving con-
traction under these conditions. Replacing tap
water with seawater would result in but a small
contraction, but doing so with waters of the
Dead Sea or of the Great Salt Lake would
cause a more significant contraction.^^
FIGURE 6.1. Elastic-contractile strip of cross-linked
poly(GVGVP) in water contracting to lift a weight
(time to half contraction: 5 minutes for millimeter
thickness,
seconds for 50)i thick fibers). (Reproduced
from Urry.^)
6.2.3 More Efficient Conversion of
Increased Salt into Motion
To this point thermal and chemical energies
have driven contraction without a change in
amino acid composition of the basic model
protein. An elastic sequence from the mam-
malian elastic fiber has been used as naturally
found, albeit a sequence separate from and syn-
6.2 Accessing Available Energies to Achieve Useful Function 221
thesized to form a 20- to 30-fold longer chain.
Now we depart from what was directly avail-
able from a natural sequence and design a
change in composition of the basic model
protein to achieve more efficient energy
conversion.
6.2.3.1
Replacing Val by Glu
The infrequent replacement of valine (Val, V)
residues by glutamic acid residues (Glu, E),
as in Polymer II in Table 6.1, replaces the
oil-like group (-CH(CH3)2) by a vinegar-like
functional group (-CH2CH2-COOH). This
introduces at physiological pH the negatively
charged carboxylate (-COO~) group. Addition
of salt (NaCl) to water results in positively
charged sodium ions (Na^) and negatively
charged chloride ions (CI"). The positively
charged sodium ions (Na^) ion pair with the
negatively charged carboxylate (-COO~)
group. Formation of the ion pairs (-COO~...
Na"^) lowers the temperature of the phase
separation from above to below the operating
temperature and drives contraction with the
moving of a weight.
As
is
apparent from Figure
5.12,
at room tem-
perature the amount of salt required to effect
the phase separation and drive contraction by
ion pairing is less than one-tenth that amount
required when there are no negatively charged
carboxylate (-COO") groups. This means a 10-
fold increase in efficiency of the function of
this salt-driven molecular machine. The simple
replacement of Val by Glu has increased the
efficiency of salt-driven contraction by more
than 10-fold (Figure 5.12).
6.2.3.2
Replacing Other Val Residues by
Phe Residues Further Increases Efficiency
Polymers III through VI represent a systematic
increase in the number of Val (V) residues
replaced by more oil-like Phe (F) residues.
Each step increase in oil-like character of the
model protein, on going from 0 to 2 to 3 to 4
and to 5 Phe residues for every 30 residues,
stepwise increases the affinity of Na^ for
-COO".
Each step increase in oil-like character
means that less of an increase in salt is required
to drive contraction. Polymer VI, when cross-
linked into elastic sheets, provides the most
efficient molecular machine of the set. This mol-
ecular machine requires less chemical energy
to produce a given amount of motion, that is,
to perform a given amount of mechanical
work.
6.2.4 Accessing Acid (Another
Form of Chemical Energy) to
Produce Motion
An even more effective way to neutralize the
affect of the vinegar-like carboxylate is to add
acid,
(H^).
This is the association of a negative
carboxylate, (-COO~) with the positive proton
(H^).
The association of proton with carboxy-
late represents a kind of ion pairing and forms
a more stable carboxyl, that is, -COO" -f- ff =
-COOH. Using Polymer II, the amount of
TABLE
6.1. The polymers (model proteins) as considered in this chapter.
Polymer
Polymer
Polymer
Polymer
Polymer
Polymer
Polymer
Polymer
Polymer
Polymer
Polymer
Polymer
I
II
III
IV
V
VI
VII
VIII
IX
X
XI
XII
(GVGVP GVGVP GVGVP GVGVP GVGVP GVGVP)4i(GVGVP)5
(GVGVP GVGVP GEGVP GVGVP GVGVP GVGVP)„(GVGVP); E/OF
(GVGVP GVGFP GEGFP GVGVP GVGVP GVGVP)n(GVGVP); E/2F
(GVGVP GVGVP GEGVP GVGVP GVGFP GFGFP)n(GVGVP); E/3F
(GVGVP GVGFP GEGFP GVGVP GVGFP GVGFP)n(GVGVP); E/4F
(GVGVP GVGFP GEGFP GVGVP GVGFP GFGFP)n(GVGVP); E/5F
(GVGVP GVGVP GKGVP GVGVP GVGVP GVGVP)n(GVGVP); K/OF
(GVGVP GVGFP GKGFP GVGVP GVGVP GVGVP)n(GVGVP); K/2F
(GVGVP GVGVP GKGVP GVGVP GVGFP GFGFP)n(GVGVP); K/3F
(GVGVP GVGFP GKGFP GVGVP GVGFP GVGFP)n(GVGVP); K/4F
(GVGVP GVGFP GKGFP GVGVP GVGFP GFGFP)n(GVGVP); K/5F
(GVGIP GVGIP GVGIP GVGIP GVGIP GVGIP)43(GVGIP)2(GVGVP)
The subscript n indicates the number of repeats of the 30 residues grounded as 6 pentamers, and n can range from 2 to
40 and more.
222
6. On the Evolution of Protein-based Machines
added acid that drives contraction is one-
thousandth the amount of salt required in the
most efficient salt-driven contraction noted
above.^^ As more Phe residues replace Val
residues, the amount of added acid required to
drive contraction becomes less and less. Finally,
with Polymer VI, a several hundred- to a
thousand-fold decrease in the amount of acid
required to drive contraction occurs.^ The effi-
ciency of the molecular machine has increased
by another several hundred to a thousand-fold.
Now, a small change in acidity from physiolog-
ical conditions can be used to drive contraction
(see Figures 1.2, 1.3, and 5.19B). Just the
common uptake of carbon dioxide from the air,
which combines with water to form carbonic
acid, or addition of a small amount of the weak
acid, for example, vinegar, becomes sufficient to
drive contraction of elastic strips of Polymer VI.
Thus, compositional changes achieved by the
simple substitution of Val by Glu and then of Val
by Phe create successively more efficient molec-
ular machines with which to produce motion. In
fact, protonation of carboxylates provides the
driving force for the propeller-like motion of
the bacterial flagella,^^ which provides the
mobiUty whereby the bacterium obtains food.
The structure of the flagellar rotary motor has
evolved to become much more complex than
our linearly contracting model proteins. A
simpler rotary motor, ATP synthase,^^ the
primary energy-converting motor of biology,
uses protonation of carboxylates to drive a
rotor that is utilized within the Fi-ATPase com-
ponent to result in the synthesis of ATP from
ADP and P.^"^ Whether it is the conversion of
chemical energy into motion or into another
form of chemical energy, we believe the under-
lying mechanism to be the same.
In our view, cyclic protonation/deprotonation
of carboxylates drives the cycUc association/
dissociation of oil-like groups responsible for
flagellar rotary motion and for rotation of an
asymmetric oil-like rotor to produce ATP by
ATP synthase. In the process, protons move
from the high concentration to the low con-
centration side of a cell membrane in which
the membrane component of the rotary motor
resides. In fact, the proton concentration
dif-
ference from one side to the other of the mem-
brane would not need to be particularly high to
drive the rotary motor. The efficiency of the fla-
geUar motor is reported to be about 50% and
that of the ATPase component of ATP synthase
operating in reverse has been calculated to
approach 80% to 100%^^ (see Chapter 8).
6.2.5 Producing Motion by
Changes in Pressure
With the above change of the aliphatic hydro-
carbon side chain of the Val (V) residue to the
aromatic hydrocarbon side chain of the Phe (F)
residue also comes the capacity for pressure
to produce motion.^^ With the correct balance
of oil-like and vinegar-like residues to set the
temperature at which oil-like separation from
water occurs, the application of pressure causes
the unfolding and setting down of a weight, and
release of pressure results in the lifting of a
weight. Remarkably, with only the conversion
of an occasional Val to Glu or an occasional
Val to Phe, both chemical energy and pressure
energy have been accessed by these protein-
based molecular machines.
6.2.6 Accessing Electrons (Electrical
Energy) to Produce Motion
6.2.6.1
Reduction of
Lysine-Attached
Nicotinamide Drives Contraction
Production of motion by the addition of elec-
trons requires attachment of vitamin-like mol-
ecules such as B2 and
B3
(see Chapters 3 and 5),
because the natural amino acids do not easily
take up and release electrons. In our experi-
mental demonstration, an N-methyl nicoti-
namide was attached to a lysine residue by the
amide moiety, and indeed reduction drove con-
traction.^^ Furthermore, increasing the oil-like
character on replacing Val (V) by Phe (F), as
with Polymers XIII, IX, and X in Table 6.1,
increases the affinity of an oxidized group for
electrons, as discussed in Chapter 5 and repre-
sented in Figure 5.19C. In the circumstance
of natural proteins, the reduction-oxidation
(redox) vitamin-like molecules bind to oppo-
sitely charged sites by ion pairing and by oil-
like associations, as discussed below.
6.2 Accessing Available Energies to Achieve Useful Function
223
6.2.6.2
Adding Positively
Charged Residues
In living organisms, the vitamin-like molecules
that accept and release electrons are commonly
negatively charged due to the presence of phos-
phate groups. Examples are phosphorylated
nicotinamide (e.g., nicotinamide mononu-
cleotide, which may be written nicotinamide-
ribose-phosphate) and flavin (e.g., flavin
mononucleotide, which may be written flavin-
pentose-phosphate). Introduction of positively
charged lysine (Lys, K) and arginine (Arg, R)
residues provides sites for binding of negatively
charged phosphate of the vitamin-derived mol-
ecules that accept and release electrons. Poly-
mers VII through XI in Table 6.1 demonstrate
the effect of an increase in the more hydropho-
bic Phe (F) residues. The increase in Phe
residues increases both the binding affinity of
the negatively charged vitamin-like nucleotide
to the positively charged protein sites and the
affinity of the vitamin-like molecules for elec-
trons.
The latter result in more efficient elec-
tron-driven molecular machines.
As was discussed in Chapter 5, for Figure
5.17, addition of electrons to a positively
charged redox group increases oil-like charac-
ter 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 elec-
tron-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.
6.2.6.3
Increasing Affinity for Electrons
Using Negatively Charged Residues
If the chemical group that can take up and
release electrons is positively charged, the same
changes in composition that increased affinity
for Na^ or H^ above become operative. In par-
ticular, if the chemical group in its electron-
deficient state were a positively charged
vitamin B3, niacin, the series of Polymers II
through VI would demonstrate a systematic
increase in affinity for the binding of positively
charged B3. Correspondingly, the stepwise
increase in oil-like character on progressing
from Polymer II to VI would also result in a
systematic increase in affinity for electrons
(see Figure 5.20C). Development of binding
capacity to a vitamin-like molecule with both
oil-like and charged components depends on
the charge and the oil-like character of the
polymer.
Alternatively, the covalent attachment of a
redox group like niacin to the lysine side chain
rather than ion-pair formation, as with Poly-
mers VII through XI in Table 6.1 and as shown
in Figure 5.20C, results in nicotinamides that
exhibit increased affinity for electrons as the
polymer contains more hydrophobic Phe
residues. Thus, stepwise increases in the oil-like
character of the polymer result in stepwise
increases in electron affinity and correspond-
ingly steeper curves indicating greater
efficiencies.
6.2.7 Accessing Light Energy to
Produce Motion
For light to be accessed to produce motion by
the consilient mechanism, there must be bound
to the model protein a group that changes its
oil-like character on absorption of a photon.
There are many ways in which this can happen.
Given the correct conditions of the solution,
even the nicotinamide considered above can
have its oil-like character changed by the
absorption of light. Another biological mole-
cule,
cinnamic acid, can be attached to a Lys
side chain to form a cinnamide. The cinnamide
is normally a linear group, but on absorption of
a photon it becomes kinked. Absorption of a
different photon can reverse the process and
straighten out the kink in the group. The linear
molecule is more oil-like than the kinked mol-
ecule.
Therefore, with the proper balance of oil-
like and vinegar-like side chains of the model
protein, absorption of the photon that straight-
ens the group can cause contraction and the
lifting of a weight, and absorption of the photon
that introduces the kink would effect the low-
ering of the weight. The principle of a Ught-
induced kink in the carotinoid of the visual
224
6. On the Evolution of Protein-based Machines
process is an important element of the energy
conversion leading to vision, as in rhodopsin of
the vertebrate eye and bacteriorhodopsin.
6.2.8 Accessing Energies to Perform
Work Other Than Motion
For electrical energy to be converted to chem-
ical energy, one need only utilize the amino acid
substitutions already considered. The presence
of a positively charged Lys residue for attach-
ment of a phosphorylated nicotinamide-ribose
group and the presence of a negatively charged
Glu or Asp w^ith the carboxylate function in
the side chain are sufficient to interconvert
electrical and chemical energy. Reduction of
the nicotinamide drives oil-like folding and
forces uptake of a proton by the carboxylate
group (see Figures 5.20A and 2.12B). This
represents the conversion of electrical energy
to chemical energy using the same groups as
are involved in mitochondria, the energy-
converting factories of the cell. Using an elastic
model protein with an adequate oil-like char-
acter and containing both a lysine-attached
N-methyl nicotinamide and a carboxylate
group, reduction of the oxidized N-methyl
nicotinamide causes the uptake of a proton.^^
Electrical energy is converted to the chemical
energy of pumping protons.
6.2.9 Summary of Minimal Amino
Acid Changes to Achieve the Diverse
Energy Conversions of Biology
Starting from the elementary elastic protein
sequence (GVGVP)n, by simple substitution,
the set of protein-based machines sufficient to
provide the set of biological energy conversions
can be achieved. It is only necessary to substi-
tute the Val (V) residue by Glu (E) and Phe
(F) and He (I) by Lys (K). Substitution by Glu
accesses chemical energy. Substitution by Phe
accesses pressure energy and increases effi-
ciency of energy conversions by the consilient
mechanism. Substitution by Lys accesses elec-
trical and light energies. The question to be
addressed now is just how difficult such substi-
tutions would be by means of evolution under
the constraints of the universal genetic code.
6.3 Mutations and Evolution of
Protein-based Machines
6.3.1 A Single Genetic Code for
All Life
All known Life is based on but a single genetic
code (see Table 6.2).^^ Because of this, all Life
would seem to be descended from a single
primitive cell. The momentous event or series
of events of Life's origin with a single genetic
code are not addressed here. From the view-
point of energy conversion, however, it would
have culminated in a moment when the
minimal set of molecular machines assembled
to form the first primitive and most competitive
self-replicating cell.
Four bases occur in the macromolecule
deoxyribonucleic acid that ultimately encode
protein sequences. They are the bases U
(uracil), C (cytosine), A (adenine), or G
(guanine), which encode for 20 amino acid
residues. They do so by means of specified
sequences of three bases called triplets. Given
four possible bases but a sequence of three
being required to specify a given residue, there
are 4^ = 4 X 4 X 4 = 64 possible triplets. Three
triplets specify the end of a protein sequence;
these are called stop codons. This leaves the
other 61 triplets to encode for 20 amino acids,
and all triplets are used. As a result, degeneracy
or redundancy occurs, that is, several different
triplets can encode for the same residue.
With all that we currently know, no com-
pelling physicochemical basis appears to exist
to explain why a particular triplet codon must
encode for a particular amino acid residue
throughout all of biology. Furthermore, why
do six different triplet codons encode for
leucine, serine, and arginine and four different
codons encode each for valine, glycine, proline,
alanine, and threonine? On the other hand, for
the standard genetic code, one triplet encodes
for tryptophan and one for methionine; two
encode for aspartic acid, glutamic acid, tyrosine,
phenylalanine, histidine, glutamine, asparagine,
lysine, and cysteine, and three triplets encode
for isoleucine. From this perspective, there
seems to be little coherence in the genetic
code.