Protein Folds: Laws of Form Revisited

Michael Denton and Craig Marshall. Protein folds: laws of form revisited. Nature. 2001 Mar 22; 410(6827):417.

From the Introduction by Giovanni Monastra, from Italy (translated from Italian by Chuck Salvo)

"The same Denton in the 80s was strongly criticized in the pages of that journal for his book Evolution, a Theory in Crisis (Burnett, London 1985): Mark Ridley in fact charged it with scant competence in its argument and of having revived old outmoded criticisms against Darwin, tantamount to saying his book could not be considered within the ambit of "serious" research on evolution (Nature, 318, 1985, pp.124-5). Well then, after about 15 years "Nature" features an article from the "reprobate" Denton in the page dedicated to innovative concepts in biology."

"To reinforce his [Denton's] doubts on the presumed central role of the genes in determining all the forms was his acquaintance in the early seventies with the neutralist theories of the Japanese biologist Kimura, much discussed at King's College. According to this theory [Kimura's], many mutations (changes in the structure of the gene and therefore in its phenotypical manifestation) are "neutral", that is neither useful nor harmful for the organism carrying it, while for classical Neodarwinism, every mutation should have a selective value, positive or negative."

"...Denton, who had never abandoned his studies on the origin of living forms, criticized with an abundance of data the Neodarwinist claim to reduce the complexity of biological change to the simplistic interplay of random mutations and natural selection."

"...he [Denton] affirmed that the laws of nature appeared structured and directed in a way specific for the self-manifestation of forms of life characterized by "rationality" such as Homo Sapiens. It is the theory of "Intelligent Design". The centrality of our species to the interior of the natural world is thus revived."

"...biological forms derive from the action of natural laws on the constituent material of life, while DNA is limited to influencing the form, but not in determining it."

From the Article:

"Just as, today, we account for the form of atoms and crystals by a set of physical laws or "constructional rules", so the pre-darwinian biologists sought to account for the origin of biological forms in terms of a set of generative physical laws often referred to as the "laws of form"."

"...recent advances in protein chemistry suggest that at least one set of biological forms -the basic protein folds- is determined by physical laws similar to those giving rise to crystals and atoms."

"During the 1970s, as the three-dimensional structure of an increasing number of folds was determined, it became apparent that the folds could be classified into a finite number of distinct structural families containing a number of closely related forms. The fact that protein folds could be classified in this manner provided the first line of evidence that the folds might be natural forms. Further evidence that the folds do indeed represent a finite set of natural forms is provided by detailed structural studies carried out over the past two decades which have revealed that the structure of the folds can be accounted for by what amounts to a set of "constructional rules" governing the way that the various secondary structural motifs, such as alpha-helices and beta-sheets, can be combined and packed into compact three-dimensional structures. One is inevitably reminded of the atom-building rules governing the assembly of subatomic particles into the 92 atoms of the periodic table."

"Consideration of these "constructional laws" suggests that the total number of permissible folds is bound to be restricted to a very small number ...Cyrus Chothia of Britain's Medical Research Council estimated that the total number of folds utilized by living organisms may not be more than 1,000. Subsequent estimates have given figures of between 500 and 1,000."


"...the fact that the total number of folds represents a tiny stable fraction of all possible polypeptide conformations, determined by the laws of physics, reinforces the notion that the folds, like atoms, represent a finite set of built-in natural forms."

"The robustness of the folds offers another clue. The fact that the folds can retain their native conformations in the face of multiple different sorts of short-term deformations caused by the molecular turbulence of the cell..."

"...the same fold can be specified by many different, apparently unrelated amino-acid sequences..."

"Finally, the fact that in many cases the same fold is adapted to very different biochemical functions is precisely what would be expected if protein functions are secondary adaptations of a set of primary, immutable, natural forms."

"If forms as complex as the protein folds are intrinsic features of nature, might some of the higher architecture of life also be determined by physical law?"

"The robustness of certain cytoplasmic forms, for example the spindle apparatus and the cell form of ciliate protozoans such as Stentor, suggests that these forms may also represent uniquely stable and energetically favoured structures specified by physical law. If it does turn out that a substantial amount of higher biological form is natural, then the implications will be radical and far-reaching... it will mean a return to the pre-darwinian conception that underlying all the diversity of the life is a finite set of natural forms that will recur over and over again anywhere in the cosmos where there is carbon-based life."