Re: God...Sort Of -- Protein Chemistry A
Mon, 9 Aug 1999 14:30:37 EDT

Greetings to One and All:

This will be the seventh of my in depth responses to Steve's post. It will
deal with questions of what constitutes a polypeptide/protein and whether
proteinoids qualify as true polypeptides/proteins.

This post will be the longest of my responses yet, since so much information
has be discussed. It is so long, in fact, that AOL has forced me to split it
into two separate parts. I apologize for the inconvenience, but I have no
choice if I am to meet Steve's requirements in this debate. I beg everyone's
further indulgence.

In the process of the doing the split, I accidentally lost everything I had
written previously for this part, so I have had to reconstruct it from
memory, which is why posting this seventh response was so long delayed. It
also means that, since I couldn't remember everything I had originally
written, I had to leave out some of what I had previously put in.

> MB>...of one of three different amino acids is added to a mix of purified
> >>amino acids and heated in a laboratory oven, then the amino acids do
> >>join. But even then they do not join to give proteins the structure they
> >>form is chemically different.
> KO>Incorrect; Fox and others have proven that thermal polyamino acids
> >are true polypeptides, that is, the amino acids form peptide bonds. That
> >is all that is needed to make a protein.
> It is Kevin who is "incorrect" here. Just producing "polypeptides" is not
> that is needed to make a protein". All proteins are polypeptides but not
> polypeptides are proteins. Proteins are a special subset of polypeptides:

In point of fact, the terms polypeptides and proteins are used
interchangeably; see below for more details. The proper term designating the
class of polymers to which polypeptides/proteins belong is polyamino acid.
As such, Steve's last two sentences, when worded properly, would read: "All
proteins are polyamino acids but not all polyamino acids are proteins.
Proteins are a special subset of polyamino acids." The products of thermal
copolymerization are often referred to as polyamino acids in recognition of
the fact that they include both polypeptides and other nonproteinous amino
acid polymers. The question then becomes whether proteinoids are true
polypeptides or some other nonproteinous polyamino acid. This question will
be delt with in the next part. In this part we have to establish a
definition of polypeptide/protein we can use.

> "Proteinous and non-proteinous amino acids, both D- and [L-] would lead to
> an indiscriminate production of polypeptides. These polypeptides would
> have scarce resemblance to protein. Protein not only requires exclusive use
> of L-amino acids, but also the use of a particular subset of only 20 amino
> acids. In addition, a biofunctional protein requires a precise sequence of
> amino acids." (Thaxton C.B., Bradley W.L. & Olsen R.L., "The Mystery of
> Life's Origin", 1992, pp 52,55).

instead of "does lead to" and "does have scarce") once again leads me to
conclude that Thaxton et al. are not presenting conclusions based on
experimental data, but are presenting personal opinion based on speculation.
In point of fact there is experimental evidence that shows that "[p]roteinous
and non-proteinous amino acids, both D- and [L-]" in fact do not "lead to an
indiscriminate production of polypeptides", and that these polypeptides in
fact bear a very strong resemblance to proteins. See S.W. Fox and K. Dose
(1977) Molecular Evolution and the Origin of Life, Revised Edition, Marcel
Dekker Publisher for more details.

In fact, Thaxton et al. state one of the diagnostic characteristics of
polypeptides/proteins (henceforth simply referred to as either polypeptides
or proteins) that is shared by proteinoids as well. To be a polypeptide a
polyamino acid must have a specific sequence and it must have a specific
function determined by its shape, which is in turn determined by its specific
sequence. Proteinoids have specific sequences, and these sequences are
highly reproducible; the same mixture of amino acids will always produce the
same limited variety of proteinoids, and each variety will have its own
specific sequence. These sequences cause proteinoids to fold into shapes
that then give them specific biofunctions, namely catalytic activity. These
functions can be eliminated when the proteinoid is denatured and can be
reacquired when the proteinoid is renatured. So far as anyone knows, only
proteins exhibit this characteristic, so any unknown biopolymer that exhibits
it is assumed to be a polypeptide until proven otherwise. Proteinoids not
only exhibit this characteristic, they are also known to be polymers of amino
acids (and only amino acids) linked together by the peptide bond (and only
the peptide bond). As I shall soon demonstrate, this last is the only other
characteristic that sets proteins apart from all other biopolymers, and it is
the one characteristic that is definitional.

As ID theorists and anti-materialists, Thaxton and Bradley have a vested
interest in placing severe, even unwarrented, restrictions on what can
constitute a protein. (I can find no information on RL Olsen, so nothing
that I am about to write should be construed in any way to apply to him/her.
For all I know he/she may be the world's leading authority on proteins,
though if that is the case, then his/her placement as third author is very
puzzling, as you will soon see.) In fact, their entire argument smacks of a
strawman. By limiting true polypeptides to modern proteins, they can argue
that any primordeal polypeptide that is not absolutely identical to proteins
must be rejected as the possible progenitor of modern proteins. This then
allows them to claim that since polypeptides identical to modern proteins
cannot be synthesized prebiotically, a materialistic explanation for the
origin of modern proteins is impossible.

Their argument suffers from two problems, though. One is a lack of
experimental evidence supporting their claim. It is based instead on
theoretical considerations (though these are undoubtedly secondary to the
philosophical considerations), but these must be tested if their critique is
to do more than simply raise questions.

The second problem is a lack of credibility. Steve is offerring Thaxton and
Bradley as if they were experts in protein chemistry, or at least
biochemistry. Compared to other ID theorists, they may very well be, but in
fact neither have any significant credentials as either biochemists or
protein chemists. According to biographies published in _The Creation
Hypothesis_ edited by J.P. Moreland and on the Discovery Institute website,
Thaxton has a PhD in organic chemistry, but has spent virtually the entirety
of his career doing philosophical study and writing. His only documented
experience in any form of biological chemistry is three years doing postdoc
work in molecular biology at Brandeis University. The same biographies state
that Bradley is an engineer and a materials scientist, and document no
experience in any form of biological chemistry. A search of MedLine for any
biology-related publications turned up nothing for a CB Thaxton and only one
publication in 1979 for a C Thaxton in x-ray crystallography. There are no
publications by a C Thaxton affiliated with Brandeis University. There is
only one publication in 1988 by a WL Bradley in the self-organization of
amino acids. In contrast, though I have only a Master's Degree, it is in
biochemistry and I have spent my entire career (over ten years) doing
biochemical and protein chemistry research. I have co-authored four papers
with a fifth in publication. As such, by comparison I myself am more of an
expert on protein chemistry than Thaxton and Bradley combined.

However, there is no need for anyone to take my word for it. Here are
statements by people who clearly are experts: biochemists, protein chemists,
molecular biologists, cell biologists and microbiologists who have written
textbooks used nationally in university courses:

"All amino acids have at least two functional groups, the alpha-carboxyl
group and the alpha-amino group. Because carboxyl groups can react with amino
groups to form amides, amino acids can combine to form long-chain polymers;
that is, proteins. A short polymer of amino acids is a peptide or
polypeptide. A protein consists of amino acids connected to one another by
amide bonds, which are known as peptide bonds when they connect amino acids.
An ionized carboxyl group (COO--) is at the C-terminal end and a protonated
amino group (NH3+) is usually at the N-terminal end of a protein. A peptide
chain typically contains one hundred or more amino acids, so that the
molecular weight of proteins can range from 10,000 (approximately sixty amino
acid residues) to several hundred thousand. Many important components of
biological systems, in addition to enzymes, are proteins." RH Abeles, PA
Frey and WP Jencks (1992) _Biochemistry_, Jones and Bartlett, pg. 42.

"In protein molecules the amino acid residues are covalently linked to form
very long, unbranched chains. They are united in a head-to-tail arrangement
through substituted amide linkages called peptide bonds that arise
by elimination of the elements of water from the carboxyl group of one amino
acid and the alpha-amino group of the next. These macromolecules, called
polypeptides, may contain hundreds of amino acid units. Some proteins contain
only one polypeptide chain; others contain two or more. The polypeptide
chains of proteins are not random polymers of indefinite length; each
polypeptide chain has a definite molecular weight, chemical composition,
sequential order of its amino acid building blocks, and three-dimensional
shape." AL Lehninger (1975) _Biochemistry_, Second Edition, Worth, pg. 57-58.

"In proteins, the alpha-carboxyl group of one amino acid is joined to the
alpha-amino group of another amino acid by a peptide bond (also called an
amide bond)....Many amino acids, usually more than a hundred, are joined by
peptide bonds to form a polypeplide chain, which is an unbranched structure.
An amino acid unit in a polypeptide is called a residue. A polypeptide chain
has direction because its building blocks have different ends--namely, the
alpha-amino and the alpha-carboxyl groups. By convention, the amino end is
taken to be the beginning of a polypeptide chain. The sequence of amino acids
in a polypeptide chain is written starting with the amino-terminal residue.
Thus, in the tripeptide alanine-glycine-tryptophan, alanine is the
amino-terminal residue and tryptophan is the carboxyl-terminal residue. Note
that tryptophan-glycine-alanine is a different tripeptide. A polypeptide
chain consists of a regularly repeating part, called the main chain, and a
variable part, comprising the distinctive side chains. The main chain is
sometimes termed the backbone." L Stryer (1981) _Biochemistry_, Second
Edition, WH Freeman, pg. 17.

"Amino acids are joined together by peptide bonds between the alpha amino
group of one amino acid and the alpha carboxyl group of a second.
Polypeptides are linear chains of amino acids, usually hundreds or thousands
of amino acids in length. Each polypeptide chain has two distinct ends, one
terminating in an alpha amino group (the amino, or N, terminus) and the other
in an alpha carboxyl group (the carboxy, or C, terminus). Polypeptides are
synthesized from the amino to the carboxy terminus, and the sequence of amino
acids in a polypeptide is written (by convenfion) in the same order. The
defining characteristic of proteins is that they are polypeptides with
specific amino acid sequences." GM Cooper (1981) _The Cell: A Molecular
Approach_, Sinauer Associates, pg. 49.

"Proteins are polymers of amino acids....Two amino acids can be joined
together via a substituted amide bond-the peptide bond. The peptide bond
forms a planar structure because of resonance stabilization, and with few
exceptions, peptide bonds assume a trans configuration. Several amino acids
can be joined together in a linear polymer to form polypeptides. The amino
acid units of a polypeptide are called residues. The residue with the free
alpha-amino group is the amino- (or N) terminal residue; the residue with the
free alpha-carboxyl group is the carboxyl- (or C) terminal residue." MA
Wells (1997) _An Electronic Companion to Biochemistry_, Cogito Learning
Media, pg. 16.

"A protein is a polymer consisting of several amino acids (a polypeptide).
Each amino acid can be thought of as a single carbon atom (the alpha carbon)
to which there is attached one carboxyl group, one amino group, and a side
chain denoted R. The side chains are generally carbon chains or rings to
which various functional groups may be attached. The simplest side chains
are those of glycine (a hydrogen atom) and alanine (a methyl group)....To
form a protein the amino group of one amino acid reacts with the carboxyl
group of another; the resulting chemical bond is called a peptide bond. Amino
acids are joined together in succession to form a linear polypeptide chain.
When the number of peptide bonds exceeds about 15 (the number is arbitrary),
the polypeptide is called a protein. The two ends of every protein molecule
are distinct. One end has a free --NH2 group and is called the amino
terminus; the other end has a free --COOH group and is the carboxyl terminus.
The ends are also called the N (or NH2) and C termini, respectively." D
Freifelder and GM Malacinski (1993) _Essentials of Molecular Biology_, Second
Edition, Jones and Bartlett, pg. 20-21.

"A covalent bond called a peptide bond forms between the amino group on one
amino acid and the carboxyl group on another amino acid. As a result of
peptide bond formation, it is possible to produce molecules varying in length
from two amino acids to chains containing thousands of them. Various terms
are used to denote the nature of compounds containing peptide bonds. Peptide
usually refers to a molecule composed of short chains of amino acids, such as
a dipeptide (two amino acids), a tripeptide (three), and a tetrapeptide
(four). A polypeptide contains an unspecified number of amino acids, but
usually has more than 20, and is often a smaller subunit of a protein. A
protein is the largest of this class of compounds and usually contains a
minimum of 50 amino acids. It is common for the terms polypeptide and protein
to he used interchangeably, though not all polypeptides are large enough to
be considered proteins." KP Talaro and A Talaro (1999) _Foundations in
Microbiology_, Third Edition, McGraw-Hill, pg. 45.

"When the amino and carboxyl groups of amino acids combine to form peptide
bonds, the constituent amino acids are termed amino acid residues. A peptide
consists of 2 or more amino acid residues linked by peptide bonds. Peptides
of more than 10 amino acid residues are termed polypeptides."
"All proteins are high-molecular-weight polypeptides. Whether a polypeptide
is termed a protein or merely a polypeptide is largely an arbitrary decision,
although the dividing line between large polypeptides and small proteins is
customarily between MW 8000 and 10,000." DW Martin Jr, PA Mayes and VW
Rodwell (1983) _Harper's Review of Biochemistry_, 19th Edition, Lange Medical
Publications, pg. 21, 31.

"Amino acids can be linked together by a reaction in which the carboxyl group
of one amino acid is joined to the amino group of another amino acid,
splitting out a molecule of water and forming a peptide bond....As more amino
acids are added to form longer chains, the products are called polypeptides.
Most polypeptides retain a free amino group at one end (called the amino
terminus or N-terminus) and a free carboxyl group at the other end (called
the carboxyl terminus or C-terminus). Protein molecules consist of one or
more polypeptide chains, each containing from a few dozen to hundreds or even
thousands of amino acids." LJ Kleinsmith and VM Kish (1995) _Principles of
Cell and Molecular Biology_, Second Edition, HarperCollins, pg. 21.

"The primary structure of a protein has been defined as the linear sequence
of amino acid residues making up the polypeptide chains of the molecule." RH
Haschemeyer and AEV Haschemeyer (1973) _Proteins: A Guide to Study by
Physical and Chemical Methods_, John Wiley and Sons, pg. 54.

Notice that none of these definitions state that proteins are made only out
of a limited number of amino acids, or that the amino acids must be of the L-
configuration. To be fair, nearly all these textbooks described modern
proteins as being made out of the same 20 L-amino acids, but they did not
define proteins as a group by this description. Note also that if any
distinction is made between polypeptides and proteins it is an arbitrary one
based on size. In fact, most of these textbooks use polypeptide and protein

So in conclusion it should now be obvious that the only feature that makes a
polypeptide/protein what it is is that it is a polymer of a specific sequence
of amino acids linked together by the peptide bond that has a specific
function. By this definition proteinoids qualify to be called thermal

Kevin L. O'Brien