Tuesday, March 25, 2008

TGD based model for the evolution of genetic code: IV

I have discussed the model for the evolution of genetic code in previous postings (I,II,III). Thanks to the Ulla Mattfolk I learned about the idea of protein folding code - something which is expected to exist but is not understood. This led to a trial for the folding code discussed in posting III and based on the assumption that aminoacid behaves like dinucleotide. This trial did not work but the learning of some basic facts about proteins and their interactions inspired second trial according to which aminoacid in the interior of aminoacid sequences behave like the conjugate of the nucleotide Y of the codon XYZ coding for it. This trial seems to work.

There exists a wonderful book "Proteins: Structures and Molecular Properties" by Thomas E. Creighton and published 1993 by W. H Freeman Company. In the following I freely refer to the general facts discussed in this book rather than referring separately to every detail. While reading this book I learned that the first guess for the code of catalysis was wrong but is also became clear what was wrong. It became clear that free aminoacid should behave like the conjugate of the DNA codon XYZ -rather than only XY- but that an aminoacid inside aminoacid sequence effectively reduces to Y since the formation of the peptide bonds by the elimination of water molecule and formation of NH---O= hydrogen bonds effectively eliminates X and Z. The ends of aminoacid behave like dicodons which conforms with their special role in biocatalysis. Only aminoacids for which Y corresponds to quarks (not antiquarks) can form hydrogen bonds so that hydrophilic-hydrophobic dichotomy corresponds to a strong matter antimatter asymmetry at quark level.

1. Matter antimatter asymmetry at the level of interactions of aminoacids

The first thing that I learned was that second nucleotide Y in the codon XYZ coding for aminoacid is what matters. Only Y=A,G aminoacid residue can form hydrogen bonds and is hydrophilic and thus interacts strongly with water and DNA and RNA. In T,C case the formation of hydrogen bonds is impossible or rare (ser,thr). In their interactions with water these aminoacids are passive, or rather-avoid water- and tend to interact with each other. This division is fundamental for the understanding of the interactions of aminoacids. The division of aminoacids to hydrophobic resp. non-hydrophobic ones corresponds to the assignment of quarks to A and G and antiquarks to T and C so that strong matter antimatter asymmetry is in question. Similar asymmetry appears in cosmology: in TGD Universe antimatter resides inside cosmic strings in the interior of big voids containing matter as galaxies at their boundaries so that one can understand why antimatter is not visible.

2. Flux tubes can connect with all electronegative atoms

Also a plausible answer to the question which atoms can be connected by flux tubes emerges.

  1. The model for dinucleotide precursor code involves precursors for which 3 precursors contain only oxygen ions or double bonded oxygens. The only possible conclusion is that oxygen can connect to any DNA letter (quark or antiquark) and that first letter-precursor correlation is a selection of the most probable alternative. Also in water oxygen atoms should form flux tube contacts with each other and aminoacids and DNA. Also nitrogen atoms could form similar flux tube connections. Same would apply to sulphur appearing in met and tyr and to electronegative atoms in general.

  2. The guess that the presence of the flux tube would be a necessary prerequisite for the hydrogen bond formation is wrong. Hydrogen bonds are formed between polar groups of hydrophilic aminoacids so that this rule does not seem to hold true. Quite generally, biologically important ions are assumed to reside as dark variants at magnetic flux tubes in the model for EEG and nerve pulse. The di-sulphur associated with cys-cys pairs play a fundamental role in protein folding. This bond is not allowed by the generalized base pairing rule which suggest that only the hydrogen bond formation which can be assigned with flux tube contacts.

  3. Hydrophobic aminoacids could connect with the oxygen in water by flux tubes but they could not form hydrogen bonds. The phase transition increasing hbar would allow them to increase their distance from water molecules in a controlled manner. This would be essential for folding and make possible the formation of pockets connected by flux tubes of large hbar to water. In quantum models for evolution of consciousness these pockets are believed to play a prominent role.

3. What can one learn from the formation of alpha helices and beta sheets?

The formation of peptide bonds by the elimination of H2O= molecules and generation of hydrogen bonds between NH and O= is an essential step in the formation of alpha helices and beta sheets. Second observation is that aminoacids decompose naturally into three parts corresponding to O=COH, R, and NH2. This suggests that aminoacid actually corresponds to the entire DNA codon XYZ coding for it. OH could correspond to Z , R to Y, and NH2 to Z. In the formation of peptide bond the flux tube connecting to COH and thus to Z would be taken by the water molecule created in the formation of peptide bond leaving only XY. The first flux tube would connect HN and O= so that X would pair with Xc assignable to O. There are no problems with the formation of bond if O= can correspond to any code letter as in the case of water. Water would correspond to matter antimatter symmetric phase and an interesting question is what counterpart this phase could have in cosmology (bosonic matter?).

The aminoacid inside protein would effectively behave like Yc in the effective base pairing. Depending on whether it corresponds to quark or antiquark, aminoacid would be hydrophilic or hydrophobic- or rather - able to form hydrogen bonds or not. Since hydrophobic aminoacids cannot form hydrogen bonds, the formation of these residue pairs would be inhibited. The hydrophilic and hydrophobic residues could tend to avoid each other and the phase transitions increasing Planck constant would make this possible. It must be emphasized that this brings in strong long range correlation between the dynamics of the aminoacid residues belonging to the first and third (second and fourth) column of the code table.

Hydrophilic aminoacids would form hydrogen bonds which each other and with DNA and RNA. In catalytic biding sites this kind of hydrogen bonds are formed between polar groups: also hydrogen bonds with water are formed and they tend to neutralize possible static charges. Ser (UCZ) and thr (ACZ) are the only effectively hydrophobic aminoacids containing OH group (and thus strictly speaking amphiphilic). Perhaps it is not an accident thr the codon ACC coding for thr appears in the stem of tRNA containing aminoacid. Ser and thr are indeed able to form hydrogen bonds with hydrophilic aminoacids and the prediction is that these aminoacids have form XGZ belonging to the last column of the code table. There are however very few biochemical reactions of this kind useful for proteins. Ser is exceptional in that it is predicted to be able to form flux tubes connecting ser_1 coded by TCZ with ser2 coded by AGZ, Z=T,C. The OH group of ser can be seen as a correlate for this property.

The aminoacids at the ends of the polymer behave effectively like dinucleotides. The aminoacid coded by XYZ would base pair like XcYc if in the beginning of polymer and to YcZc if at the end of polymer. These nucleotides should have very special selective role in DNA-aminoacid and RNA-aminoacid interactions. Remarkably, it is known that the cutting of COOH and NH2 away from the end of polymer in general makes protein folding impossible (also mutations can affect dramatically folding). The first nucleotide of protein is usually met containing sulphur and the conjugation associates met with stop and tyr codons. The association of met with stop is indeed natural for the free NH2 of met having no hydrogen bond in the beginning of the sequence.

According to Creighton, the binding sites of catalyst and ligand in the reaction complex are conjugates both geometrically and physically. It would be nice to have a concrete representation of this conjugacy in terms of the genetic code. Geometric conjugacy is easy to understand in terms of the lock and key picture but I am not quite sure what physical conjugacy could mean. Standard physics intuition would suggests that hydrophilic aminoacids that behave as acids resp. bases attract each other. This option does not possess any obvious formulation in the proposed picture. Matter antimatter conjugation for the second nucleotide Y of XYZ looks however very natural so that the aminoacids in the first and third (second and fourth) row of the code table would tend to pair with each other. This mechanism might be flexible enough to allow to find a conjugate of a given binding site by trial and error. The interpretation would be that hydrophobia tends to create concave and hydrophily convex structures. The attraction between Y and Yc in the braided conjugate regions would due to the Coulomb interaction between quark and antiquark at the ends of the wormhole flux tube.

The strong correlation between RNA dinucleotide and aminoacid in the case of tRNA conforms with this picture. The third flux tube associated with the aminoacid could connect with the third codon after the transition to RNA-aminoacid era. During RNA era tRNA2 would have connected the O=C-OH part of the aminoacid to water molecule.

4. Interactions with DNA

Also in the interactions with DNA and RNA the aminoacid in the interior of the sequence would base-pair" like Yc. The original idea about molecular sex would transform in the sense that the companion of the hydrophilic aminoacid would DNA nucleotide in general. Hydrophobic aminoacids would behave like hermits. The generic contacts with DNA would be contacts with single nucleotide and there would be 4 different basic contacts. Aminoacids are indeed known to form contacts with single nucleotide. Hydrophilic contacts would be favored and hydrophobic contacts avoided so that again Y=A,G aminoacids would play at the outer boundary of DNA would play the active role. The aminoacids inside a given column of the code table would interact in very much the same manner with DNA nucleotides as far as formation of hydrogen bonds is considered. The terminals of the protein polymer are predicted to behave like XcYc resp. YcZc if the corresponding codon is XYZ. Again only hydrophilic codons are expected to be able to form hydrogen bonds. N-terminal is usually met and met and should avoid DNA.

5. Interactions of proteins with ions and electrons

Proteins interact also with electrons and ions. Typical process are the addition or removal of proton, electron, ion such Ca++, or molecule such as O2. These interactions are not well understood. For instance, the interactions involve the transfer of electrons between ligand protein and protein inducing oxidation (electron is given), reduction (electron is received) or redox reaction (both reduction and oxidation take place). In metabolism redox process is central. These reactions are reversible and it is difficult to understand how electrons are able make their long journey from the interior of the ligand so fast and avoiding dissipative effects. The formation of cyclotron Bose-Einstein condensates and electronic Cooper pair condensates at the magnetic flux tubes connecting ligand and protein could be the solution of the mystery.

6. How DNA nucleotides are connected with the hydrophilic ends of lipids?

The starting point of all these developments was the model for DNA as topological quantum computer (tqc) described in the earlier postings I, II, III, IV, V, VI, VII, VIII, IX, X, XI, XII, XIII.

It was assumed that braid strands defined by "wormhole magnetic" flux tubes join nucleotides to lipids and can continue through the nuclear or cell membrane but are split during tqc. The hydrophilic ends of lipids attach to water molecules and self-organization patterns for the water flow in gel phase induce a 2-D flow in the lipid layer which is liquid crystal defining tqc programs at the classical level as braidings. The flow indeed induces braiding if one assumes that during topological computation the connection through the cell membrane is split and reconnected after the halting of tqc.

The challenge is to understand microscopically how the flux tube joins DNA nucleotide to the phospholipid. What is clear that the points at which the flux tubes attach should be completely standard plugs and the mechanism giving rise to polypeptids is an excellent guide line here. Recall that phospholipid, the dancer, has two hydrophobic legs and head. Each leg has at the hydrophilic end O=C-O-C part joining it to glyceride connected to monophosphate group in turn connected to the hydrophilic residue R. The most often appearing residues are serine, inositol, ethanolamine, and choline. Only three of these appear in large quantities and there is asymmetry between cell exterior and interior.

Let us denote by =O1 and =O2 the two oxygens in question (analogs of right and left hemispheres!). The proposal is that DNA nucleotide and =O1 are connected by a flux tube: the asymmetry between right and left lipid legs should determine which of the legs is "left leg" and which O= is the "left brain hemisphere". =O2, the holistic "right brain hemisphere", connects in turn to the flux tube coming from the other symmetrically situated =O2 at the outer surface of the second lipid layer. During tqc this flux tube is split or disappears. The lipid residue R couples with the flow of the liquid in gel phase. Since =O is in question the quark or antiquark at the end can correspond to the DNA nucleotide in question. Also the necessary complete correlation between quarks and antiquark charges at the ends of flux tubes associated with =O1 and =O2 can be understood as being due to the minimization of Coulomb interaction energy.

The phosphate groups associated with nucleotides of DNA strand contain also =O, which could act as a plug to which the flux tube from the nucleotide is attached. =O appears in biomolecules involved with varying functions such as signalling, control, and metabolism. =O might act as a universal plug to which flux tubes from electronegative atoms of information molecules can attach their flux tubes. This would also provide a concrete realization of the idea that information molecules (neurotransmitters, hormones) are analogous to links in Internet (see this): they would not represent the information but establish a communication channel. The magnetic flux tube associated with the information molecule would connect it to another cell and by the join to =O plug having flux tube to another cell, say to its nucleus, would create a communication or control channel.

To repeat the earlier statement, this proposal for the folding code - or rather, the code of entire biocatalysis - is so beautiful that it deserves to be killed: this should be easy for a professional biochemist. If the hypothesis survives, it would provide a royal road to the understanding of the catalytic bio-chemistry.

For details see the chapter Prebiotic Evolution in Many-Sheeted Space-time of "Genes and Memes".

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