Naked Science Forum
Non Life Sciences => Physics, Astronomy & Cosmology => Topic started by: puppypower on 31/01/2016 13:13:25
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Here is an idea that came to me a few days ago. If you look at an atom, the electrons occupy orbitals. The atomic orbitals will define the probability of finding an electron over time. The nucleus of atoms is in the center of each orbital shape.
(https://www.learner.org/interactives/periodic/images/ch_2_p_orbital.jpg)
The nucleus maintains its positional probability, with much tighter tolerance. In other words, it is far easier to know where the nucleus is than where an electron is, since the electron occupies an extended space defined by the orbital. This difference can be correlated to mass, with the higher mass of the nucleus adding inertia, which prevents the nucleus, from moving around as easily, based on EM potential. The electron is very light and can move quickly with the same EM potential.
If you look at life, life has a tendency to narrow and even remove probability functions, compared to non-life. For example, proteins fold into perfect folds that are not governed by the law of statistics. The folds of large complex protein have a probability of 1.0.
Proteins are held together with weak secondary binding forces that are easy to denature; disrupt. Even though thermal agitation in the water should be enough energy to add randomness to protein folds, due to this weak secondary binding, randomness is not observed. The protein will fold the same way each time. It defies the laws of statistics.
Another related observation is the left handedness of protein in cells. Beyond the constraints of life, protein tend to form both left and right handed helixes, in equal proportions. This is like throwing a two sided dice, with heads and tails coming up with equal probability. But with life, heads; left, comes up thousands of time in a row. The odds of thousands of heads in a row, means the is no longer gambling, but has become a sure thing; loaded coin.
The question becomes, since life depends heavily, on hydrogen bonding to act as bridges between atoms and molecules, and since the hydrogen proton is on the nucleus side, instead of the electron side (see first paragraph) is the mass of the hydrogen bond, causing probability to tighten up?
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In a word, no. Protein folding obeys the rules of stereochemistry: atoms know nothing of statistics.
If you completely denature a protein, or any other molecule, it won't necessarily reform in its original configuration, but if some key parts of the structure remain intact, it will generally revert to a semblance of the original.
The principle of indeterminacy holds for nuclei as well as electrons Δp.Δx = h/2π. It just happens that as p is 1800 times larger for a proton, Δx is going to be a lot smaller for any fractional indeterminacy of p.
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Beyond the constraints of life, protein tend to form both left and right handed helixes, in equal proportions.
No, they don't.
A "racemic" equal mixture of left and right-handed proteins created by non-biological processes don't form a helix at all (or other common protein components like sheets).
They tend to form a "blob".
It is thought that complex life could use predominantly left-handed, or predominantly right-handed proteins (chiral proteins), but a racemic mixture would not form the complex protein structures that we see on Earth. The mystery for the start of life on Earth is how the observed chiral proteins could form out of the presumed original racemic mixture.
The few right-handed proteins (http://en.wikipedia.org/wiki/Chirality_(chemistry)#D-amino_acid_natural_abundance) we see are somewhat toxic (some appear in antibiotic compounds, others in scented compounds that might repel insects).
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Protein folding in cells fold with probability equal to 1.0. The folding is not governed by statistics. This has been known of 50 years. The protein will fold the same way each time. Statistics is a tool; hammer, and not a fact of nature. The hammer is still being used to set a screw, when it is not the right tool.
Let us look a little deeper into the subcellular world down to the level of the protein molecules – the building blocks that make up the enzyme complexes responsible for the biochemical reactions. It has been known since the early work of Kauzmann (1959) and Tanford (1968) on the thermodynamics and kinetics of protein denaturation, that proteins are not very stable. In thermodynamic terms, the stabilities lie in the range 20 – 60 kJ/mol. However, H-bond energies are quoted also in the range 12 – 38 kJ/mol (Fersht, 1999). Comparing these figures, one is struck by their apparent incongruity – they mean that protein stability relies on a few H-bonds. It is even conceivable that some H-bonds are more stable than small proteins. For example, Finney (1982) gives the stability of lysozyme and ribonuclease as equivalent to 4 H-bonds each. One naturally asks, how can a molecule containing thousands of atoms be held together by a few H-bonds? I am not saying that these figures are wrong, but rather that another energetic mechanism for protein stability has to be found – one that has not been detected by classical methods.
One is reminded here of the problem of protein folding. As I have pointed out elsewhere (Watterson, 1997), that problem also arises from applying classical theories, since they predict an average, not a unique fold. That these questions remain unsolved still today after 50 years of intense research effort, highlights a two-fold failing of statistical methods: firstly, they did not predict the existence of a stable folded state, and secondly, once given as an experimental fact, they cannot explain it.
http://www1.lsbu.ac.uk/water/watterson.html
A folding protein contains thousands of atoms, with the final folded protein very weakly held together, with the binding strength equivalent of a couple of hydrogen bonds. Yet, experiments, as far back as 50 years ago, demonstrated that in spite of this meta-table situation, protein will still fold with unique folds. This was not predicted by statistical models, nor has it be explained in 50 years with such models. This is being ignored by statistical models, which act like it was not there. Most students never know the facts, due to misinformation; traditions.
The goal of this topic was not to argue the facts, but to accept the facts like any good scientific will, and try to explain it in a simple way. I prefer be ahead of the curve, and not on the wall pouring hot oil on the facts, even if this is how the system rewards you. Science is about truth and not money and traditions. Maybe I am wrong about that?
A protein is like a long chain with side groups sticking out along the length of the chain. The long chain is bound together by peptide linkages; covalent bonds. The chain then forms a left handed helix along the backbone, that is bond together with weaker hydrogen bonding. This is shown below.
(https://www.thenakedscientists.com/forum/proxy.php?request=http%3A%2F%2Fwww.chemguide.co.uk%2Forganicprops%2Faminoacids%2Fahelix.gif&hash=49a51332e37fe9d4a6df54ff1428d257)
The side groups are varied and each type will have their own potential. This will cause the backbone helix to fold. This it can form a blob. But this blob folds the same way every time, any cell makes that same protein. This situation looks like it should be random in terms of folding due to the weak binding, but observations have shown this not government by statistics. This has been known for 50 years. I am not here to argue the fact versus monopoly traditions, but rather to take the lead and explain how this may be possible. The future is already defined the facts.
I was using the observation that the mass and inertia of atomic nuclei, makes it easier to locate the nucleus of an atom compared to the more mobile electron. The mass and inertia of the nucleus causes the electrons to move in space using this as the center; gas in motion. The electrons do not lead but will follow.
Life uses hydrogen bonding, which adds the extra mass and inertia of hydrogen proton, between the electron clouds of various atoms. This helps to direct divergent electrons to this center of mass. The properties of life are dependent on hydrogen bonding, wth life showing us signs; perfect folding, it is not concerned with statistics. Statistics means more, if we look at the electrons. Life appears to think in terms the hydrogen core which is more about tighter tolerance.
Maybe before we can do further, we need to address why for 50 years, key data has been ignored. Once this is settled, then there will be need. If it is not broken, don't try to fix it. We need to show it is broken, first, then we can fix it.
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The side groups are varied and each type will have their own potential. This will cause the backbone helix to fold.
Computer models are not very good at predicting the shape of folded proteins.
The online game "foldit (http://en.wikipedia.org/wiki/Foldit)" has human players manipulating proteins to identify the likely shape. The computer calculates a "score" for the energy of the folded protein. This human-assisted protein folding has been credited with identifying several previously unknown protein structures.
Apparently, foldit is now being upgraded to assist design of small-molecule drugs whose interactions with proteins can be modeled.
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Proteins do NOT fold into a specific shape with a probability even close to 1.
Synthesis of a polypeptide chain does not guarantee that the chain will fold into what would be the "correct" shape of the protein as produced in a cell. A whole range of foldamers (peptides with the same sequence of amino acids, but folded differently) will be sampled. Sometimes there are one or two foldamers that are thermodynamically preferred over the others, but there will still be a distribution.
Taking a protein of the "correct" shape and denaturing it (pushing it to sample more foldamers than it would in biological setting) usually ruins the shape permanently (it rarely goes back to the original shape), even if no covalent bonds are broken.
In biological systems, the shape of a protein is usually templated and/or shepherded into the right conformation by many other proteins, co-factors, ions, etc., and even then there is a not-insignificant rate of misfolding. Usually the organism has ways of detecting misfolded proteins and destroying (or fixing) them, but sometimes mis-folded proteins accumulate and lead to diseases (https://en.wikipedia.org/wiki/Proteopathy)
Let us also note that proteins are rarely static in biological systems. That proteins change conformations allows them to be "active" machines with the organism (gates open and close, enzymes "turn on" and "turn off", some of them even "walk" https://en.wikipedia.org/wiki/Kinesin).
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Another related observation is the left handedness of protein in cells. Beyond the constraints of life, protein tend to form both left and right handed helixes, in equal proportions. This is like throwing a two sided dice, with heads and tails coming up with equal probability. But with life, heads; left, comes up thousands of time in a row. The odds of thousands of heads in a row, means the is no longer gambling, but has become a sure thing; loaded coin.
The handedness of helices in proteins is determined by the chirality of the amino acids themselves. Natural amino acids are all of the same configuration, so it is not surprising that this chirality manifests in the secondary and tertiary structures of proteins.