Thermodynamic molecular switch in biological systems

It is, of course, known that most living systems can live and operate optimally only at a sharply defined temperature, or over a limited temperature range at best. This implies that many basic biochemical interactions exhibit a well-defined Gibbs free energy minimum as a function of temperature. Most typical processes of biological molecules or biopolymers show ΔH°(T) positive (unfavorable) and also a positive ΔS°(T) (favorable) at low temperature, due to a positive (ΔCp°/T). For biological systems ΔG°(T) shows a complicated behavior, wherein ΔG°(T) changes from positive to negative, then reaches a negative value of maximum magnitude, and finally becomes positive as temperature increases. This communication demonstrates that the critical factor is a temperature-dependent ΔCp°(T) (specific heat capacity change) of reaction that is positive at low temperature but switches to a negative value at a temperature well below the ambient range. This thermodynamic molecular switch determines the behavior patterns of the Gibbs free energy change, and hence a change in the equilibrium constant, Keq, and/or spontaneity. The subsequent, mathematically predictable changes in ΔH°(T), ΔS°(T), ΔW°(T) and ΔG°(T) give rise to the classically observed behavior patterns in biological reactivity as demonstrated in three interacting protein systems—human DNA ligase I–DNA polymerase β, the fragment complementation reaction of S-protein-phe 13-S-peptide (M13F-RNase S′), and glucagon trimerization. In cases of protein unfolding such as the phage T4 phage lysozyme temperature-sensitive mutants, no thermodynamic molecular switch is observed.