Here’s That Protein-Protein Interaction Problem

as to:

of course another problem is that it is astronomically difficult for evolution to evolve a single protein to begin with, let alone meaningful interaction sites.

with 'astronomically difficult', 'Dr. Hunter used the exactly correct term:

"a very rough but conservative result is that if all the sequences that define a particular (protein) structure or fold-set where gathered into an area 1 square meter in area, the next island would be tens of millions of light years away." Kirk Durston Evolution vs. Functional Proteins ("Mount Improbable") - Doug Axe and Stephen Meyer – Video https://www.youtube.com/watch?v=7rgainpMXa8

Even the numbers from Darwinists themselves agree with the 'astronomically difficult' assessment for Darwinian processes producing a single functional protein

Now Evolution Must Have Evolved Different Functions Simultaneously in the Same Protein - Cornelius Hunter - Dec. 1, 2012 Excerpt: In one study evolutionists estimated the number of attempts that evolution could possibly have to construct a new protein. Their upper limit was 10^43. The lower limit was 10^21. These estimates are optimistic for several reasons, but in any case they fall short of the various estimates of how many attempts would be required to find a small protein. One study concluded that 10^63 attempts would be required for a relatively short protein. And a similar result (10^65 attempts required) was obtained by comparing protein sequences. Another study found that 10^64 to 10^77 attempts are required. And another study concluded that 10^70 attempts would be required. In that case the protein was only a part of a larger protein which otherwise was intact, thus making the search easier. These estimates are roughly in the same ballpark, and compared to the first study giving the number of attempts possible, you have a deficit ranging from 20 to 56 orders of magnitude. Of course it gets much worse for longer proteins. http://darwins-god.blogspot.com/2012/12/now-evolution-must-have-evolved.html?showComment=1354423575480#c6691708341503051454

And as Dr. Hunter also alluded to, even if you could find a functional protein, once you have a protein it is extremely difficult to modify it into a different function:

For instance, most proteins are not highly modifiable. You can’t just randomly go about swapping in different amino acids. Protein function typically degrades rapidly with amino acid substitutions.

A few notes along this line:

Stability effects of mutations and protein evolvability. October 2009 Excerpt: The accepted paradigm that proteins can tolerate nearly any amino acid substitution has been replaced by the view that the deleterious effects of mutations, and especially their tendency to undermine the thermodynamic and kinetic stability of protein, is a major constraint on protein evolvability,, http://www.ncbi.nlm.nih.gov/pubmed/19765975 The Evolutionary Accessibility of New Enzyme Functions: A Case Study from the Biotin Pathway - Ann K. Gauger and Douglas D. Axe - April 2011 Excerpt: We infer from the mutants examined that successful functional conversion would in this case require seven or more nucleotide substitutions. But evolutionary innovations requiring that many changes would be extraordinarily rare, becoming probable only on timescales much longer than the age of life on earth. http://bio-complexity.org/ojs/index.php/main/article/view/BIO-C.2011.1/BIO-C.2011.1 When Theory and Experiment Collide — April 16th, 2011 by Douglas Axe Excerpt: Based on our experimental observations and on calculations we made using a published population model [3], we estimated that Darwin’s mechanism would need a truly staggering amount of time—a trillion trillion years or more—to accomplish the seemingly subtle change in enzyme function that we studied. http://www.biologicinstitute.org/post/18022460402/when-theory-and-experiment-collide From Thornton's Lab, More Strong Experimental Support for a Limit to Darwinian Evolution - Michael Behe - June 23, 2014 Excerpt: In prior comments on Thornton's work I proposed something I dubbed a "Time-Symmetric Dollo's Law" (TSDL).3, 8 Briefly that means, because natural selection hones a protein to its present job (not to some putative future or past function), it will be very difficult to change a protein's current function to another one by random mutation plus natural selection. But there was an unexamined factor that might have complicated Thornton's work and called the TSDL into question. What if there were a great many potential neutral mutations that could have led to the second protein? The modern protein that occurs in land vertebrates has very particular neutral changes that allowed it to acquire its present function, but perhaps that was an historical accident. Perhaps any of a large number of evolutionary alterations could have done the same job, and the particular changes that occurred historically weren't all that special. That's the question Thornton's group examined in their current paper. Using clever experimental techniques they tested thousands of possible alternative mutations. The bottom line is that none of them could take the place of the actual, historical, neutral mutations. The paper's conclusion is that, of the very large number of paths that random evolution could have taken, at best only extremely rare ones could lead to the functional modern protein. http://www.evolutionnews.org/2014/06/more_strong_exp087061.html podcast - Michael Behe: The Limit in the Evolution of Proteins (Thorton's 2014 paper) http://intelligentdesign.podomatic.com/entry/2014-07-09T16_35_28-07_00

And then there is the problem that is NEVER addressed by Darwinists of 'what do you do with a protein once you got it?' There are approx. 20, 000 types of a billion trillion protein 'building blocks' in a human body. What in blue blazes is directing all these proteins to work in harmony. Talbott puts the problem like this:

HOW BIOLOGISTS LOST SIGHT OF THE MEANING OF LIFE — AND ARE NOW STARING IT IN THE FACE - Stephen L. Talbott - May 2012 Excerpt: “If you think air traffic controllers have a tough job guiding planes into major airports or across a crowded continental airspace, consider the challenge facing a human cell trying to position its proteins”. A given cell, he notes, may make more than 10,000 different proteins, and typically contains more than a billion protein molecules at any one time. “Somehow a cell must get all its proteins to their correct destinations — and equally important, keep these molecules out of the wrong places”. And further: “It’s almost as if every mRNA [an intermediate between a gene and a corresponding protein] coming out of the nucleus knows where it’s going” (Travis 2011),,, Further, the billion protein molecules in a cell are virtually all capable of interacting with each other to one degree or another; they are subject to getting misfolded or “all balled up with one another”; they are critically modified through the attachment or detachment of molecular subunits, often in rapid order and with immediate implications for changing function; they can wind up inside large-capacity “transport vehicles” headed in any number of directions; they can be sidetracked by diverse processes of degradation and recycling... and so on without end. Yet the coherence of the whole is maintained. The question is indeed, then, “How does the organism meaningfully dispose of all its molecules, getting them to the right places and into the right interactions?” The same sort of question can be asked of cells, for example in the growing embryo, where literal streams of cells are flowing to their appointed places, differentiating themselves into different types as they go, and adjusting themselves to all sorts of unpredictable perturbations — even to the degree of responding appropriately when a lab technician excises a clump of them from one location in a young embryo and puts them in another, where they may proceed to adapt themselves in an entirely different and proper way to the new environment. It is hard to quibble with the immediate impression that form (which is more idea-like than thing-like) is primary, and the material particulars subsidiary. Two systems biologists, one from the Max Delbrück Center for Molecular Medicine in Germany and one from Harvard Medical School, frame one part of the problem this way: "The human body is formed by trillions of individual cells. These cells work together with remarkable precision, first forming an adult organism out of a single fertilized egg, and then keeping the organism alive and functional for decades. To achieve this precision, one would assume that each individual cell reacts in a reliable, reproducible way to a given input, faithfully executing the required task. However, a growing number of studies investigating cellular processes on the level of single cells revealed large heterogeneity even among genetically identical cells of the same cell type. (Loewer and Lahav 2011)",,, And then we hear that all this meaningful activity is, somehow, meaningless or a product of meaninglessness. This, I believe, is the real issue troubling the majority of the American populace when they are asked about their belief in evolution. They see one thing and then are told, more or less directly, that they are really seeing its denial. Yet no one has ever explained to them how you get meaning from meaninglessness — a difficult enough task once you realize that we cannot articulate any knowledge of the world at all except in the language of meaning.,,, http://www.netfuture.org/2012/May1012_184.html#2

Of related note:

“Although living things occupy a three-dimensional space, their internal physiology and anatomy operate as if they were four-dimensional. Quarter-power scaling laws are perhaps as universal and as uniquely biological as the biochemical pathways of metabolism, the structure and function of the genetic code and the process of natural selection.,,, The conclusion here is inescapable, that the driving force for these invariant scaling laws cannot have been natural selection.” Jerry Fodor and Massimo Piatelli-Palmarini, What Darwin Got Wrong (London: Profile Books, 2010), p. 78-79

bornagain77

July 11, 2014

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Of note, The difficulty of developing a single protein-protein binding site is put at 10^20 replications of the malarial parasite by Dr. Behe. This number comes from direct empirical observation. Yet, protein-protein interactions appear to be very rarely conserved across species: What Evidence Is There for the Homology of Protein-Protein Interactions? - 2012 Excerpt: Protein-protein interactions appear to be very rarely conserved unless very high sequence similarity is observed. Consequently, inferred interactions should be used with care… Conclusion excerpt: Using this framework, we are able to estimate interactome sizes with a method that is different from others in the literature. Our estimates for the fraction of conserved interactions are very low for definitions of homology that are often associated with the transfer of functional annotations across species. We emphasise that our results will be overestimates due to the preferential investigation of homologous proteins in multiple species.,,, We urge extreme caution in interpreting interactions transferred across species unless the definition of homology employed is a strict one, and we believe that interactome incompleteness is not solely responsible for the lack of observed conservation of interactions. http://www.ploscompbiol.org/article/info%3Adoi%2F10.1371%2Fjournal.pcbi.1002645 Moreover, there is, 'surprisingly', found to be 'rather low' conservation of Domain-Domain Interactions occurring within Protein-Protein interactions: A Top-Down Approach to Infer and Compare Domain-Domain Interactions across Eight Model Organisms Excerpt: Knowledge of specific domain-domain interactions (DDIs) is essential to understand the functional significance of protein interaction networks. Despite the availability of an enormous amount of data on protein-protein interactions (PPIs), very little is known about specific DDIs occurring in them.,,, Our results show that only 23% of these DDIs are conserved in at least two species and only 3.8% in at least 4 species, indicating a rather low conservation across species.,,, http://www.plosone.org/article/info:doi/10.1371/journal.pone.0005096 And yet, Dr. Behe, on the important Table 7.1 on page 143 of Edge Of Evolution, finds that a typical ‘simple’ cell might have some 10,000 protein-binding sites. Whereas a conservative estimate for protein-protein binding sites in a multicellular creature is,,, Largest-Ever Map of Plant Protein Interactions - July 2011 Excerpt: The new map of 6,205 protein partnerings represents only about two percent of the full protein- protein "interactome" for Arabidopsis, since the screening test covered only a third of all Arabidopsis proteins, and wasn't sensitive enough to detect many weaker protein interactions. "There will be larger maps after this one," says Ecker. http://www.sciencedaily.com/releases/2011/07/110728144936.htm So taking into account that they only covered 2%, of the full protein-protein "interactome", then that gives us a number, for different protein-protein interactions, of 310,000. Thus, from my very rough 'back of the envelope' calculations, we find that this is at least 30 times higher than Dr. Behe's estimate of 10,000 different protein-protein binding sites for a typical single cell (Page 143; Edge of Evolution; Behe). Therefore, at least at first glance from my rough calculations, it certainly appears to be a fantastically impossible step that evolution cannot make, by purely unguided processes, to go from a single cell to a multi-cellular creature or to transmutate one creature into another creature. Dr. Behe's empirical research agrees with what is found if scientists try to purposely design a protein-protein binding site: Viral-Binding Protein Design Makes the Case for Intelligent Design! - Fazale Rana - June 2011 Excerpt: When considering this study, it is remarkable to note how much effort it took to design a protein that binds to a specific location on the hemagglutinin molecule. As biochemists Bryan Der and Brian Kuhlman point out while commenting on this work, the design of these proteins required: "...cutting-edge software developed by ~20 groups worldwide and 100,000 hours of highly parallel computing time. It also involved using a technique known as yeast display to screen candidate proteins and select those with high binding affinities, as well as x-ray crystallography to validate designs.2" If it takes this much work and intellectual input to create a single protein from scratch, is it really reasonable to think that undirected evolutionary processes could accomplish this task routinely? In other words, the researchers from the University of Washington and The Scripps Institute have unwittingly provided empirical evidence that the high-precision interactions required for PPIs requires intelligent agency to arise. http://www.reasons.org/viral-binding-protein-design-makes-case-intelligent-design-sick-coolbornagain77

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