Cell Language Theory, The: Connecting Mind And Matter

94 The Cell Language Theory: Connecting Mind and Matter

b2861 The Cell Language Theory: Connecting Mind and Matter “6x9”

(2) The substrates bind only to the stable Franck–Condon states of

enzymes, E*, and not to its ground state, E. This contrasts with the

traditional induced-fit hypothesis of Koshland [28]. To highlight this

difference, the Franck–Condon principle-based mechanism of ligand

binding is referred to as the “pre-fit” hypothesis (Section 3.2.9).

(3) Enzyme-catalyzed chemical reactions can occur only at the unstable

Franck–Condon state, denoted as E‡ and enclosed within the square

brackets, [...].

(4) The energy stored in E* at state b is thermally derived and hence

cannot be utilized to do any useful work lest the Second Law of

Thermodynamics is violated, but the energy stored in E* at state c is

derived from the free energy of binding of S to E* and thus able to

do work either internally (e.g., modulation of the rate of electronic

transition) or externally on enzyme’s environment as in myosin head

exerting a force on the actin filament (Figure 3.49).

(5) The transition from a to c (without being mediated by state b) is what

is involved in the Circe mechanism of enzymatic catalysis as proposed

by Jencks [74]. Since this mechanism is not based on the GFCP, the

Circe effect mechanism may be viewed as theoretically incomplete.

3.2.13 The Information–Energy Complementary Landscape

Theory of Protein Folding

The field of protein folding appears to have gone through a paradigm shift

around 1995, spearheaded by Wolynes et al. [184] and Dill and Chan

[185], fulfilling the earlier theoretical speculations of Harrison and Durbin

[186]. The paradigm shift involves replacing the idea of folding pathways

with the so-called “folding funnel” (see below). In other words, the earlier

notion of a denatured protein folding to its final native conformation

through a series of distinct intermediate conformational states has been

replaced by a new view, according to which an ensemble of conforma-

tional isomers (often called “conformers”, not to be confused with “con-

formons”; one conformer can carry or be associated with a set of

conformons) of a denatured protein undergoes a transition to a final native

conformation through a series or “ensembles” of conformational interme-

diates, each intermediate following a unique folding path to the final

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