My book, “Molecular Theory of the Living Cell: Concepts, Molecular Mechanisms, and Biomedical Applications,” was published by Springer, New York, in April, 2012. This book summarizes the results of my four decade-long search for the molecular principles underlying the living cell and took four years to be written. One of the most surprising findings is that a mathematical equation, referred to as the blackbody radiation-like equation (BRE), fits (i) protein folding Gibbs free energy data of the 4,300 proteins of E. coli (see the right-hand panel of Figure 1 shown below), (ii) the single-molecule enzymic activity of cholesterol oxidase (Section 11.3.3), and (iii) the whole-cell transcription rate and transcript level data measured from budding yeast undergoing glucose-galactose shift (Section 12.12). Because the mathematical form of BRE is identical to that of the blackbody radiation equation discovered by M. Planck in 1900 which later led to the quantization of the energy of electrons in atoms, it appears logical, by analogy, to postulate that the Gibbs free energy levels of enzymes in living cells are also quantized. The quantization of the energy levels of electrons in atoms accounted for the structural regularities of matter embodied in the periodic table. Similarly the discovery of BRE and the consequent quantization of Gibbs free energy of enzymes in living cells (Section 12.14) may account for the functional regularities of living cells and their higher-order structures including the human body. Just as the 1.25-page Nature article published by Watson and Crick in 1953 found the secrets of life in the form of the DNA double helix, so it may be that the 730-page Molecular Theory of the Living Cell published this year has found a secret of the living cell in the form of BRE (see Figure 1 and Table 1 below).
The fitting of biological data to BRE demonstrated in this book has a two-fold significance: i) molecular and cell biology are connected to quantum mechanics (see the atom-cell isomorphism postulate in Section 10.5), and ii) the quantization of Gibbs free energies of biopolymers inside the cell accounts for the stability of the physical and chemical processes that underlie cell functions. These ideas can be schematically represented as shown below (see also the cell force described in Section 12.13):
(Quantization of the energy of electrons in atoms) —> (Quantization of Gibbs free energy of biopolymers in living cells) —> (Dynamic steady states, also called ‘cell orbitals’, of intracellular physical and chemical processes) —> (Cell functions).
DNA is often referred to as the book of life. In the same vein, the agent that reads and effectuates the instructions written therein must be identified with the living cell which is life itself. The former is metaphorical but the latter is real (see the second to the last row in Table 1 below). In this table, the relation between DNA and the cell is analyzed and characterized in the light of the new developments in molecular cell biology summarized in Molecular Theory of the Living Cell.
|Table 1. A comparison between DNA molecule and the living cell|
|Volume (nm3)||~103||~ 109|
|Complexity (Relative)||1||~ 106|
|Structure||Static structure(Equilibrium structure)||Static and dynamic structures (Dissipative structure)|
|Principle||Watson-Crick base pairing,
Double helix (Visualizable, geometrical)
|Blackbody radiation-like equation (BRE) applicable to 1) protein folding, 2) single-molecule enzymology, 3) whole cell transcription rates, and 4) whole-cell RNA levels.
|Principle discovered||in 1953||in 2008-9|
|Metaphor||Book of Life||Life Itself
(i.e., the reader and executioner of the book of life)
|Embodiment of||Genetic Information||Organized Molecular Motions driven by Information-Energy, also called Ggnergy (see Section 2.3.2).|
The theoretical curve fits the empirical data almost perfectly except toward the tail end where the theoretical curve rises above the empirical one. The area between these two curves is estimated to be about 5% of the total area which would correspond to approximately 200 proteins. These proteins may have thermodynamic properties that cannot be estimated by their chain length, N, alone and implicate other factors such as conformational strains (referred to as conformons in Chapter 8 and as frustrations by P. W. Anderson) that raise the ground-state free energy levels and hence reduce the associated activation free energies for the denaturation of these proteins.