AgnosticWeb.com - Life's biochemical complexity: folding

Life's biochemical complexity: folding (reply)

David Turell — Fri, 23 Jan 2015 01:06:45 +0000

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.

Life\'s biochemical complexity: folding (reply)

David Turell — Sun, 03 Feb 2013 15:54:01 +0000

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

David Turell — Sat, 03 Nov 2012 15:23:49 +0000

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 Â¼ 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.