Linguistics, Semiotics, and Philosophy - Molecular Theory of the Living Cell - page 157

biophysicists working in the field of protein folding that 3-dimensional folds of
proteins should be ultimately predictablebasedontheiraminoacidsequence
information alone, the view being referred to as the Anfinsen's dogma (Newman
and Bhat 2007) in analogy to the Central Dogma in molecular biology (see Sect.
11.1 ) . Anfinsen's dogma is based on Anfinsen's discovery in 1954 of the sponta-
neous refolding of ribonuclease A after denaturation. He found that the enzyme
refolded into its native conformation if the environmental conditions employed
were carefully controlled, that is, if the denaturant urea was removed before
2-mercaptoethanol, but the enzyme did not refold correctly if the order of remov-
ing the denaturants were revered. As will be discussed in Sect. 11.1 , Anfinsen's
dogma may not be fully supported by more recent experimental findings.
Valencia's pessimistic conclusion regarding protein structure-function correla-
tion reminded me of a similar situation that transpired between the sixteenth and
the mid-nineteenth century in the field of the theory of algebraic equations
(Aleksandrov et al. 1984, pp. 261-278, Vol. I). The following is a list of the key
events in the development of the theory of algebraic equations:

1. Ferrari (1522-1565) solved the general fourth-degree (i.e., quartic) polynomial
equation of the type, x 4 +ax 3 +bx 2 +cx+d 0 in the radical form (i.e.,

including the square root of n, where n is a positive number).
2. In 1824, Abel (1802-1829) proved that the fifth-degree (i.e., quintic) polynomial
equations could not be solved in the radical form.
3. In “Memoir on the conditions of solvability of equations in radicals” published
in 1846, Galois (1811-1832) explained why the quintic or higher-order polyno-
mial equations cannot be solved in radicals. In the process, Galois was led to
formulate a new mathematical theory, that is, the group theory, which has since
been found to apply to a wide range of mathematical problems, providing a
universal organizing principle in modern mathematics .

¼

It is interesting to note that it took three centuries for mathematicians to realize
that, although the fourth- and lower-order polynomial equations could be suc-
cessfully solved in radical forms, the fifth- and higher-order ones could not be so
solved. The reason for this was found to be that the coefficients of the quintic and
higher-order equations belonged to a different field than the field to which the
quartic and lower-order equations belonged, the former field being insoluble and
the latter solvable (thus constituting the so-called Galois group )( http://en.
wikipedia.prg/wiki/Galois_theory ) . Similarly, based on the experimental and
theoretical evidences that have accumulated during the latter decades of the
twentieth century and the first one of the twenty-first, I came to the conclusion
between 2005 and 2009 that, even though the 2-D structures (i.e., -helices and

a

-sheets) of proteins can be largely determined based on amino acid sequences
alone, the 3-D and higher-order structures of proteins might not be so determined
because the 3-D and higher-order structures of proteins are functions not only of
their amino acid sequences but also of the time- and space-dependent microenvi-
ronmental conditions inside the cell under which proteins fold. A similar idea was

b