Life\'s biochemical complexity (Introduction)

by David Turell @, Saturday, November 03, 2012, 15:23 (4404 days ago)

I've reviewed an article on protein complexity in a living cell. There is the issue of the exact order of the amino acids, the exact folding, and the fact that a single cell may have 4,500 different protein molecules. The complexity is such that the authors consclude one protein molecule if left to its own devices could not self-assemble in the time since the Big Bang.-The article is: The Levinthal paradox of the interactome-"Unlike protein folding, self-assembly of the
interactome has not yet prompted such widespread
attention, and for understandable reasons. It is a
problem of bewildering complexity, far more challenging
than the beguiling simplicity of two-state
proteins like ribonuclease that can self-assemble in
vitro."-"Levinthal's calculation2 assumed nine possible configurations
for each /,w-pair in the backbone (three
staggered configurations for each rotatable bond,
like ethane), resulting in 9^100 = 10^95 possible conformations
for a chain of 100 residues. Given the time
required for single bond rotations (picoseconds),
even a small protein that initiated folding by random
search at the time of the big bang would still be
thrashing about today"-"For n ¼ 4500, this is on the order of 10^7200, an
unimaginably large number; but a more realistic calculation
is yet more complicated. With an average of
3540 distinct interfaces for a single protein, there
are 4500 x 3540 = 1.6 x 10^7 entities, resulting in
10^5.4x10^7 possible distinct interaction patterns (cf.
Supporting Information). If proteins are present in
3000 copies instead of a single copy, identical pairwise
complexes of the same pair should not add to
multiplicity of interactions patterns; nevertheless,
the number of distinct interactomes increases further
because different copies of the same protein can
engage in interactions with different partners at the
same time. In this case, the estimated number of
different interactomes is on the order of 10^7.9x10^10"-Luckily, as the authors point out, life makes life.

Life\'s biochemical complexity: folding

by David Turell @, Sunday, February 03, 2013, 15:54 (4312 days ago) @ David Turell

Another complex article on the importance of protein folding. Long strings of amino acids must have the proper fold to function-"Nature has come up with an enormous variety of protein three-dimensional structures, each of which is thought to be optimized for its specific function. A fundamental biological endeavor is to uncover the driving evolutionary forces for discovering and optimizing new folds. A long-standing hypothesis is that fold evolution obeys constraints to properly fold into native structure."-"Nature has shaped the make up of proteins since their appearance, 3.8 billion years ago. However, the fundamental drivers of structural change responsible for the extraordinary diversity of proteins have yet to be elucidated"-http://www.ploscompbiol.org/article/info%3Adoi%2F10.1371%2Fjournal.pcbi.1002861#pcbi.1002861-Wang2-No protein 3.8 billion years ago! Only life makes proteins of the size in this study. All by chance according to atheists.

Life's biochemical complexity: folding

by David Turell @, Friday, January 23, 2015, 01:06 (3594 days ago) @ David Turell

Folding prevents knotting, but requires exact sequences of amino acids:-http://physics.aps.org/synopsis-for/10.1103/PhysRevLett.114.028102-"Everyday experience shows that strings easily knot. Preventing this requires careful folding or winding when stowing away. Molecular ropes, like polymer chains, can suffer the same fate, but that is not true for biopolymers like proteins and DNA; despite their complex folded conformations, they rarely get knotted. A new study by Thomas Wüst from the Swiss Federal Institute of Technology (ETH), Zurich, and colleagues suggests the differences in the interactions between different parts of the chain of a protein (due to the sequence of amino acids forming it) is what controls and prevents knotting.-"Wüst et al. simulated simplified, coarse-grained proteins made of 500 monomers (“residues”), which were either hydrophobic or polar. The authors compared different types of sequences: homoresidue chains, randomly ordered ones, and chains designed with specific repetition patterns, calculating their various ground-state conformations and checking for knots. They found that the knottiness of the chain depended on the sequence, and they were able to design sequences that were either highly knotted or almost completely knot-free. Sequences that were free of knots typically produced neatly folded, locally ordered structures, with none of the extended loops seen in the knotted sequences.-"The proteins and sequences investigated here are much simpler than real proteins, which are made of twenty amino acids, rather than two. However, the authors speculate that sequence could have been a controlling factor in the evolution of proteins, allowing them to evolve towards knot-free conformations that can reliably perform their functions."-For a polymer of 500 amino acids, the odds of getting it right are 1 in 20^500. Life must have been so easy to start.

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