96 The Cell Language Theory: Connecting Mind and Matterb2861 The Cell Language Theory: Connecting Mind and Matter “6x9”the difference between the final and initial states), which becomes ∆G =
∆E – T∆S, if the pressure–volume work is negligible in protein folding, it
would follow that, at some point along the vertical axis of the folding fun-
nel, the free energy decrease, i.e., –∆G, due to energy decrease, i.e., –∆E,
should exactly cancel out the free energy increase, +∆G, due to entropy
decrease, –∆S, so that ∆G = 0. At this point, protein folding process stops
and an equilibrium state is reached.
The folding funnel theory as now formulated seems to lack the biologi-
cal dimension, because the theory seems to be based on the fundamental
assumption that protein folding is determined by the tendency of a protein
to minimize its free energy content (cf., the “principle of minimal frustra-
tions” [188]), in contrast to the more likely possibility that proteins in living
cells have been selected by evolution, not based on free energy minimiza-
tion, but rather based on their biological functions, regardless of their free
energy levels. Their biological functions in turn would be determined by
their three-dimensional molecular shapes. It may be possible to expand the
two-dimensional folding funnel diagram (Figure 1 in [184]), consisting of
the y-axis encoding energy and the x-axis (i.e., the width of the funnel)
encoding entropy, by adding the z-axis perpendicular to the xy-plane to
accommodate the effects of biological evolution (i.e., genetic information)
on protein folding. In this manner, it should be possible to incorporate the
effects of biological evolution into the protein folding process.
The “folding funnel” model of protein folding is also called “energy
landscape” model. One way to incorporate biological evolution (and
hence genetic information) into the energy landscape theory of protein
folding may be to identify the topology (i.e., surface shape) of the energy
landscape as the medium for encoding the effects of biological evolution.
Although I have no proof, it seems to me that there may be a good correla-
tion between the degree of the bumpiness (measured by, say, the number
of the bumps and associated valleys of the folding funnel which together
serve as the kinetic barriers for entrapping sequence-specific conforma-
tional strains, i.e., “conformons” [65] or “frustrations” [188]) of the
energy landscape and the genetic information encoded in amino acid
sequence of proteins. It may be speculated that the bumpier the surface of
the energy landscape of a protein, the higher its information content (of
the Hartley type [189]).b2861_Ch-03.indd 96 17-10-2017 11:46:25 AM