Equilibrium thermodynamics and the genesis of protein–protein complexes in cells

It is often thought that the structural complexity of living organisms places Life outside the laws of Physics. According to the Second Law of Thermodynamics, inanimate matter tends towards ever-increasing randomness. Most thermodynamic studies on the living system are course-grained in the sense that it is the whole organism which is considered and they lack microscopic details. In these studies, as the living system is an open system, non-linear thermodynamics have been used. This requires that a number of assumptions be made concerning the living system itself, which may not be correct in organisms living under natural environmental conditions. In the present study, we depart from this approach and use a fine-grained analysis of the genesis of subcellular protein complex structures. The analysis is performed in terms of classical equilibrium thermodynamics using the acquired knowledge of protein/protein interactions. In this way, it is demonstrated that the spontaneous creation of ordered subcellular structures occurs in accordance with the Second Law of Thermodynamics. We specifically consider the simple example of protein dimer and trimer formation from its monomer components, both in vitro and with chaperone assistance in vivo. The entropy decrease associated with protein complex assembly, on which the continuing debate is founded, is shown to be a relatively small component in the overall and positive entropy increase. Graphic abstract: [Figure not available: see fulltext.].