Biochemistry Question for Group

On Fri, 13 Feb 2004 06:04:47 +0000 (UTC),

TomHendricks474 said:

This is one of those IF...THEN questions.

IF we have a strand of RNA that has a loose end, the 3' end that goes many bases beyond any base
pairing,

AND IF this loose end is made up of only G and A bases or purine bases.

AND IF the carboxyl end of a peptide, is h-bonded to any one of these purines - (let's use for
example either GGG or GAG bases, with the h-bond to the middle G or A)

In an aqueous solution (i.e., lots of water) you can NOT form stable hydrogen bond between a free
amino acid and a single-stranded polynucleotide. Such hydrogen bonds would have to compete with
equivalent hydrogen bonds to water molecules. Since the concentration of water molecules is a
million times greater than the concentration of amino acids or bases, there won't be any of the
"bonding" that your "theory" requires.

Furthermore, even if such hydrogen bonds were stable there is still the problem of specificity. Each
amino acid has a number of different hydrogen bond donors and acceptors and each base has several
different potential hydrogen bonding sites. Take adenylate as an example. If we look only at the
base part (and not the sugar or phosphate groups) then there are three potential hydrogen bond
acceptors at N1, N3, and N7 and two potential hydrogen bond donors on the amino group. (Not counting
alternatate tautomers of adenine.) The total number of possible different hydrogen bonds between an
amio acid and an adenylate residue is at least a dozen and could be a lot more depending on the
amino acid side chain. None of these bonds will have a significant half-life in aqueous solution.

Your crazy "theory" is inconsistent with known chemistry and biochemistry. You need to learn about
reaction rates and basic thermodynamics. (I haven't even mentioned the fact that the -COOH group
doesn't exist on free amino acids in solution.)

In order to get specific hydrogen bonding of the sort you require, you have to create a hydrophobic
environmment and binding sites that position the molecules in the proper relationship. In the case
of free amino acids interacting with a polynucleotide this would require a large protein with a
complex binding site for polynucleotide and amino acids. In that case, it's the binding protein that
confers the specificity and not the polynucleotide.

Forget about hydrogen bonds. It's much easier to envisage a primitive enzyme that creates a covalent
bond between a free amino acid and the end of a polynucleotide chain. This primitive enzyme would be
the ancestor of all amino acid snthetases. The enzyme can be specific because it has binding sites
that will only bind certain amino acids and certain polynucleotides. The covalent bond it creates is
stable in agueous solution. As an added bonus, it could "activate" the amino acid for subsequent
peptide bond formation.

Larry Moran

[email hidden] (TomHendricks474) wrote in message news:<[email hidden]>...

Quoted message said:

This is one of those IF...THEN questions.

IF we have a strand of RNA that has a loose end, the 3' end that goes many bases beyond any base
pairing,

AND IF this loose end is made up of only G and A bases or purine bases.

AND IF the carboxyl end of a peptide, is h-bonded to any one of these purines - (let's use for
example either GGG or GAG bases, with the h-bond to the middle G or A)

THEN would that set up, or support, or favor, a specific chirality in the peptide bond?

An RNA strand is chiral, due to the D-ribose. Even if it weren't, any genetic polymer with a loose
end would be chiral. There are thousands of ways in which one chiral molecule could impose chirality
on a collection of racemic molecules by some kind of catalytic action.

The particular way you have in mind seems particularly inappropriate. You should probably want to
hypothesize that h-bonding between amino acid and base involves the amino group, as well as the
carboxyl group. In that way, you are engaging the chirality of the amino acid in the relationship.

<< Forget about hydrogen bonds. It's much easier to envisage a primitive enzyme that creates a
covalent bond between a free amino acid and the end of a polynucleotide chain. This primitive enzyme
would be the ancestor of all amino acid snthetases. The enzyme can be specific because it has
binding sites that will only bind certain amino acids and certain polynucleotides. The covalent bond
it creates is stable in agueous solution. As an added bonus, it could "activate" the amino acid for
subsequent peptide bond formation.

TH But that presents a problem. If you have a covalent bond between amino acids, and that between
amino acids and certain polynucleotides, then breaking one would break the other. And because of
their stability its difficult to have variants. Also why would polynucleotides need protein in the
first place?

Also I was hoping you would answer my hypothetical question about IF the aa and a base sequence such
as GGG or GAG would h-bond (under any stable condition) would it set up a specific chirality?
Whether its likely or not, I'd like to find out.

Larry Moran

<< An RNA strand is chiral, due to the D-ribose. Even if it weren't, any genetic polymer with a
loose end would be chiral. There are thousands of ways in which one chiral molecule could impose
chirality on a collection of racemic molecules by some kind of catalytic action.

The particular way you have in mind seems particularly inappropriate. You should probably want to
hypothesize that h-bonding between amino acid and base involves the amino group, as well as the
carboxyl group. In that way, you are engaging the chirality of amino acid in the relationship.

Quoted message said:

Quoted message said:

Tom: Could you carry this idea further just a bit. If b Z*oth ends involved then what?

[email hidden] (TomHendricks474) wrote in message news:<[email hidden]>...

Quoted message said:

<< An RNA strand is chiral, due to the D-ribose. Even if it weren't, any genetic polymer with a
loose end would be chiral. There are thousands of ways in which one chiral molecule could impose
chirality on a collection of racemic molecules by some kind of catalytic action.

The particular way you have in mind seems particularly inappropriate. You should probably want to
hypothesize that h-bonding between amino acid and base involves the amino group, as well as the
carboxyl group. In that way, you are engaging the chirality of amino acid in the relationship.

Quoted message said:

Quoted message said:

Tom: Could you carry this idea further just a bit. If both ends involved then what?

I don't understand the question. Also, I find on reflection that I was wrong in a part of my
original post. An achiral genetic polymer with a loose end is NOT NECESSARILY chiral. And, if we are
talking about something made of stacked Watson-Crick base pairs with a hypothetical achiral backbone
running perpendicular, then chirality probably exists due to base sequence even without loose ends.

Sorry for creating the confusion.

Incidentally, Larry Moran is 100% right. You really ought to listen to him. Study some chemistry. A
person who hopes to make a breakthru in OOL chemistry should have been able to point out my error.
He should not be asking for help on questions of elementary chemistry (and then ignoring the
responses if he doesn't like them).

<< In an aqueous solution (i.e., lots of water) you can NOT form stable hydrogen bond between a free
amino acid and a single-stranded polynucleotide. Such hydrogen bonds would have to compete with
equivalent hydrogen bonds to water molecules. Since the concentration of water molecules is a
million times greater than the concentration of amino acids or bases, there won't be any of the
"bonding" that your "theory" requires.

TH Accepting the above, then this type of bonding could only happen in the dry phase of a heat
cycle, or in water if and only if it somehow was protected from the water.

LM Furthermore, even if such hydrogen bonds were stable there is still the problem of specificity.
Each amino acid has a number of different hydrogen bond donors and acceptors and each base has
several different potential hydrogen bonding sites.

TH This presents problems for sure. At first I would think that any h-bonding in a dry phase would
help in thermal stability, and allow those molecules to last another day. IF my scenario has any
truth, then there must have been a selective advantage for the h-bonding to be in the way I
suggested. Another thing this suggests is that, in a heat cycle we have a dry phase where there are
numerous h-bonded variants, and a wet phase where all these h-bonds are severed. Thus each day in
the cycle we have numerous variants or hybrids for selection. This makes more sense than a single
fluke event like most scenarios have.

LM Take adenylate as an example. If we look only at the base part (and not the sugar or phosphate
groups) then there are three potential hydrogen bond acceptors at N1, N3, and N7 and two potential
hydrogen bond donors on the amino group. (Not counting alternatate tautomers of adenine.) The total
number of possible different hydrogen bonds between an amio acid and an adenylate residue is at
least a dozen and could be a lot more depending on the amino acid side chain. None of these bonds
will have a significant half-life in aqueous solution.

Your crazy "theory"

TH I consider it an hypothesis.

LM is inconsistent with known chemistry and biochemistry. You need to learn about reaction rates and
basic thermodynamics. (I haven't even mentioned the fact that the -COOH group doesn't exist on free
amino acids in solution.)

In order to get specific hydrogen bonding of the sort you require, you have to create a hydrophobic
environmment and binding sites that position the molecules in the proper relationship. In the case
of free amino acids interacting with a polynucleotide this would require a large protein with a
complex binding site for polynucleotide and amino acids. In that case, it's the binding protein that
confers the specificity and not the polynucleotide.

TH I think if the conditions above are correct, then my scenario is indeed wrong. Yet I think in the
earliest times of the origin, I don't think the above applies.

LM Forget about hydrogen bonds. It's much easier to envisage a primitive enzyme that creates a
covalent bond between a free amino acid and the end of a polynucleotide chain. This primitive enzyme
would be the ancestor of all amino acid snthetases. The enzyme can be specific because it has
binding sites that will only bind certain amino acids and certain polynucleotides. The covalent bond
it creates is stable in agueous solution. As an added bonus, it could "activate" the amino acid for
subsequent peptide bond formation.

TH But this just presents more problems than answers for many reasons. Perhaps the most important is
this Why would a polynucleotide chain need connections to an amino acid, or vice versa? If you
respond with 'it was a fluke' then we have yet another fluke moment in the OOL. That kind of 'many
random fluke events' scenario, just does not make any sense to me at all.

On Tue, 17 Feb 2004 18:05:03 +0000 (UTC),
TomHendricks474 <[email hidden]> wrote:

Larry Moran said:

Quoted message said:

In an aqueous solution (i.e., lots of water) you can NOT form stable hydrogen bond between a free
amino acid and a single-stranded polynucleotide. Such hydrogen bonds would have to compete with
equivalent hydrogen bonds to water molecules. Since the concentration of water molecules is a
million times greater than the concentration of amino acids or bases, there won't be any of the
"bonding" that your "theory" requires.

Accepting the above, then this type of bonding could only happen in the dry phase of a heat cycle,
or in water if and only if it somehow was protected from the water.

Hydrogen bonds won't form in any kind of "dry phase" that I could imagine. The second part of your
statement is correct.

Quoted message said:

Quoted message said:

Furthermore, even if such hydrogen bonds were stable there is still the problem of specificity.
Each amino acid has a number of different hydrogen bond donors and acceptors and each base has
several different potential hydrogen bonding sites.

This presents problems for sure.

That's a mild way of putting it.

Quoted message said:

At first I would think that any h-bonding in a dry phase would help in thermal stability, and
allow those molecules to last another day. IF my scenario has any truth, then there must have been
a selective advantage for the h-bonding to be in the way I suggested.

Why not just admit that your "theory" is ridiculous?

Quoted message said:

Another thing this suggests is that, in a heat cycle we have a dry phase where there are numerous
h-bonded variants, and a wet phase where all these h-bonds are severed. Thus each day in the cycle
we have numerous variants or hybrids for selection. This makes more sense than a single fluke
event like most scenarios have.

Nothing about your "theory" makes sense.

Quoted message said:

Quoted message said:

Take adenylate as an example. If we look only at the base part (and not the sugar or phosphate
groups) then there are three potential hydrogen bond acceptors at N1, N3, and N7 and two
potential hydrogen bond donors on the amino group. (Not counting alternatate tautomers of
adenine.) The total number of possible different hydrogen bonds between an amio acid and an
adenylate residue is at least a dozen and could be a lot more depending on the amino acid side
chain. None of these bonds will have a significant half-life in aqueous solution.

Quoted message said:

Your crazy "theory"

I consider it an hypothesis.

You could call it wild uniformed speculation.

Quoted message said:

Quoted message said:

is inconsistent with known chemistry and biochemistry. You need to learn about reaction rates and
basic thermodynamics. (I haven't even mentioned the fact that the -COOH group doesn't exist on
free amino acids in solution.)

Quoted message said:

In order to get specific hydrogen bonding of the sort you require, you have to create a
hydrophobic environmment and binding sites that position the molecules in the proper
relationship. In the case of free amino acids interacting with a polynucleotide this would
require a large protein with a complex binding site for polynucleotide and amino acids. In that
case, it's the binding protein that confers the specificity and not the polynucleotide.

I think if the conditions above are correct, then my scenario is indeed wrong. Yet I think in the
earliest times of the origin, I don't think the above applies.

That's the nature of crazy theories. They don't have to agree with facts.

Quoted message said:

Quoted message said:

Forget about hydrogen bonds. It's much easier to envisage a primitive enzyme that creates a
covalent bond between a free amino acid and the end of a polynucleotide chain. This primitive
enzyme would be the ancestor of all amino acid snthetases. The enzyme can be specific because it
has binding sites that will only bind certain amino acids and certain polynucleotides. The
covalent bond it creates is stable in agueous solution. As an added bonus, it could "activate"
the amino acid for subsequent peptide bond formation.

But this just presents more problems than answers for many reasons. Perhaps the most important is
this Why would a polynucleotide chain need connections to an amino acid, or vice versa?

To activate the amino acid for peptide bond formation, for one thing.

Quoted message said:

If you respond with 'it was a fluke' then we have yet another fluke moment in the OOL. That kind
of 'many random fluke events' scenario, just does not make any sense to me at all.

I understand. You prefer the perfectly sensible idea that the temperature of the ocean (or a small
puddle) could fluctuate between 100C and 60C every day for thousands of years.

Larry Moran