Life\'s biochemical complexity (Introduction)

by David Turell , Saturday, November 03, 2012, 15:23 (4380 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.