Experimental Proof of Intelligent Design for the Amateur Scientist

Dr. Azo Mazur
Fellow of the reDiscovery Institute

Proceedings of the Chemical Society of Pierce County, 2005

Reprinted in The reDiscovery Institute Proceedings, 2006


Protein Sequence. Lost in Space

Proteins are the traffic signals and drawbridges of biology, and the concrete and rebar, too. Proteins are long linear chains of amino acids that fold into well-defined "native states".

Although sometimes disguised, one of the most common arguments we hear against Darwinianism is the vanishingly small chance that a given protein - with a specified sequence of amino acids - would be found in an mixture of random-sequence proteins. With 20 amino acids, there are 20x20=400 possible dipeptides (composed of two amino acids). There are 20x20x20 possible tripeptides. For the average human protein (estimated to be 469 amino acids in length, Pruess et al., 2003), the number of possible amino acid sequences is 20^469 (20 raised to the 469 power) which is big big big number, much bigger than the 10^500 limit of my HP 48G calculator. Protein 'sequence space' is a vast. You would not want to be lost there.

If you and I and our families and friends and their families and their friends started randomly combining amino acids hoping to stumble upon a 469 amino acid protein of specified sequence, we would never, never, never, not in a billion billion years, never, never, ever succeed. Even if we had enough time, the earth would run out of carbon before we slogged our way out of that vast random sequence space. Most possible proteins have not been made, neither by nature nor in the laboratory, and never will be made. Protein sequence space is essentially unexplored.

We know the amino acid sequences of all human proteins. Where did those sequences come from? How did nature get the right sequences? Could evolution have found a path through the wilderness of random sequence space to arrive at just the human sequences we observe? We know one thing for sure: the path could not have been random. The essential impossibility that a human protein could have been obtained by random joining of amino acids is well known, and even applies to people who think they have only 12 different amino acids.

The essential impossibility that even one human protein could arise by random association of amino acids is the very core of the "Design Inference". This point has been articulated best by my nephew 'Little Willie Dembski' (he is very sweet in private), who says that we should "infer Intelligent Design when an observed event has low probability of occurring under all the non-design hypotheses." Little Willie has invented something he calls 'Specified Complexity', which is defined by a criterion of improbability. For an event to have Specified Complexity, its probability of occurance by random events must be lower than his Universal Probability Bound, which Little Willie sets at one in 10^150 (10 raised to the 150 power). The random synthesis of the average human protein of 469 amino acids of specified sequence meets that standard hands down, with hundreds of zeros to spare.

How sad that none of us were to watch the Intelligent Designer make the first human protein. We will never know how it was done. But do we have to look back through the fog of time, to ancient prehistory, to find the only evidence of Design? No, we can see Intelligent Design happening, in real time, right here, right now.

Protein Folding. This is the Jupiter II

Think again about our average human protein of 469 amino acids, with specified sequence. Let's assume that by the miracle design process the correct amino acid sequence was assembled so that our protein can function, as an enzyme or in a structural capacity. But wait, and wait some more, and sorry, keep waiting... each amino acid has two rotatable bonds, known as phi and psi (ignore that this is a wild underestimate because it neglects sidechain conformations). Each of those bonds can assume three possible rotations (called rotameric states). Therefore a protein of 469 amino acids has 3^469 possible conformational states (10^223 states). Since bonds change their rotational state about 10 times in a picosecond, our average human protein of 469 amino acid will take 10^202 years, or 10^193 billion years, to fold, to randomly find that one single conformational state known as the native state. The chance that the average human protein will fold by random processes during the 10 billion year existence of the universe is way way way less than the Little Willie's Universal Probability Bound. This little secret is known to biochemists, who do not talk about it to outsiders, as the 'Levinthal Paradox' (Voet and Voet, 2004).

A protein with the correct amino acid sequence is only functional when properly folded. All proteins must fold into their native states (amyloid diseases are caused by misfolded proteins.) But you don't have time, life does not have time, even Little Willie Dembski does not have time, to wait for proteins, randomly stumbling around in conformational space, to find their native conformations.

Little Willie tells us that "exhausting of probabilistic resources [is a] reason to postulate nonmaterial intervention." What he means in this context is that if a protein folds (converting from random conformation to native state), which has a very very very (keep going) low probability of occurring, then God did it it must be by the hand of the Intelligent Designer. Protein folding requires an Intelligent Designer - every protein, every time it folds. Every protein has to leap over Little WIllie's Universal Probability Bound to fold into its native state.

Like I say to Little Willie nearly every day, OK Little Willie, let's stop that tedious theorizing and hectoring, and LET'S DO AN EXPERIMENT! Why bother with a theory, I always ask him, if you are too lazy to make specific testable predictions with it? After enough of this, I finally got tired of waiting and did it myself. The Azo Mazur Prediction: At least some denatured proteins (which are lost in random conformational space) under some circumstances, can fold to their single native states. If so, proteins can hurdle Little Willie's Universal Probability Bound. And I will have demonstrated the existence of the Intelligent Designer (and will start looking for cheap tickets to Stockholm for my Nobel Prize).

We can denature a protein, that's easy, say by heating it. Heat turns a protein loose in that vast wilderness of random conformational space. Then we can cool it down, and watch it to see what happens. We can watch to see whether it flops around forever in the vastness of random conformation space, or whether the Intelligent Designer will take our protein by the hand and hoist it over Little Willie's Universal Probability Bound, back to its single native state. If we can demonstrate that a denatured protein folds, that it can find that one correct conformation out of all those gazzilion times gazzilion times gazzilion (keep going) incorrect possible conformations then we will have demonstrated Intelligent Design.

Experiment. Prove the existence of God, Father of Jesus Christ our Savior the Intelligent Designer in your own kitchen.

Experimental Procedure
(keep a lab notebook, write down your observations, wear safety goggles, work with a partner)

1) Order a sample of BPTI (small cheap pure protein, $130.00 from Sigma-Aldrich, $3.49 plust $126.51 S&H from the reDiscovery Institute).
2) Add PBTI to salty water (not too salty).
3) Heat BPTI solution to 90*C (this denatures the BPTI, best not to boil).
4) Allow your BPTI solution to cool slowly to room temperature (this is where the Intelligent Designer might step in to fold the PBTI).
5) Bring BPTI solution to local chemistry department and request a Circular Dichroism Spectrum (tell them Dr. Mazur sent you).

If CD shows native state (it will), you have proven the existence of an Intelligent Designer.

Study Questions
1) Someone might argue that if a protein can leap over Little Willie's Universal Probability Bound in a couple of hundred milliseconds, then it is not very Universal, is not much of a Bound and is based on phony Probabilities. How do you respond?
(answer: Only a Blue State Secularist would say something like that.)

2) Someone might argue it is not reasonable to assume random searches of protein sequence space (in evolution) or conformational space (in protein folding), and that Little Willie Dembski is an idiot. How do you respond?
(answer: Only a Blue State Secularist would say something like that.)

3) Someone might argue that because the probability of being dealt any specific 13 card bridge hand is around one in a trillion, that it is impossible to play bridge. How do you respond?
(answer: Only a Blue State Secularist would say something like that.)


References
Pruess, M., Fleischmann, W., Kanapin, A., Karavidopoulou, Y., Kersey, P., Kriventseva, E., Mittard, V., Mulder, N., Phan, I., Servant, F., & Apweiler, R. "The Proteome Analysis database: a tool for the in silico analysis of whole proteomes" (2003) Nucleic Acids Res 31, 414-7.

Voet, D. and Voet, J.G., Biochemistry, 3rd Edition, John Wiley & Sons, New York, 2004.

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