Arrow of Time, Entropy, and Protein Folding: Holistic View on Biochirality

Abstract

Chirality is a universal phenomenon, embracing the space–time domains of non-organic and organic nature. The biological time arrow, evident in the aging of proteins and organisms, should be linked to the prevalent biomolecular chirality. This hypothesis drives our exploration of protein aging, in relation to the biological aging of an organism. Recent advances in the chirality discrimination methods and theoretical considerations of the non-equilibrium thermodynamics clarify the fundamental issues, concerning the biphasic, alternative, and stepwise changes in the conformational entropy associated with protein folding. Living cells represent open, non-equilibrium, self-organizing, and dissipative systems. The non-equilibrium thermodynamics of cell biology are determined by utilizing the energy stored, transferred, and released, via adenosine triphosphate (ATP). At the protein level, the synthesis of a homochiral polypeptide chain of L-amino acids (L-AAs) represents the first state in the evolution of the dynamic non-equilibrium state of the system. At the next step the non-equilibrium state of a protein-centric system is supported and amended by a broad set of posttranslational modifications (PTMs). The enzymatic phosphorylation, being the most abundant and ATP-driven form of PTMs, illustrates the principal significance of the energy-coupling, in maintaining and reshaping the system. However, the physiological functions of phosphorylation are under the permanent risk of being compromised by spontaneous racemization. Therefore, the major distinct steps in protein-centric aging include the biosynthesis of a polypeptide chain, protein folding assisted by the system of PTMs, and age-dependent spontaneous protein racemization and degradation. To the best of our knowledge, we are the first to pay attention to the biphasic, alternative, and stepwise changes in the conformational entropy of protein folding. The broader view on protein folding, including the impact of spontaneous racemization, will help in the goal-oriented experimental design in the field of chiral proteomics.

Fundamental Cause of Bio-Chirality: Space-Time Symmetry—Concept Review

“…The biological systems, representing thermodynamically open non-equilibrium states characterized by the bio-molecular phase transitions, are commonly associated with symmetry transformations (symmetry changes or "breaking") [165][166][167][168] and not trivial bidirectional behavior of entropy [123,171]. Notably, the evolution of galaxy clusters exhibits similar bi-directional (decreasing and increasing stages) entropy patterns [43,[172][173][174]. The fundamental significance of biochirality at the molecular and cellular levels assumes the mechanisms of the organism/brain morphology, behavior, cognition, and consciousness are grounded on basic principles of spatial organization and function.…”

Enigma of Pyramidal Neurons: Congruence to Molecular, Cellular, Physiological, Cognitive and Psychological Function

“…From the top view, the hierarchical structure is the chain of downstream processes, including motor functions, perceptual abilities, neuronal circuits, and underlying molecular biology. Interpreting sensory perception and motor functions within cellular and molecular biology relies significantly on the laws of space-time symmetry [12,[26][27][28][29]. Following this logic, the shape and functions of PyrNs deserve specific attention.…”

In Planta, In Vitro and In Silico Studies of Chiral N6-Benzyladenine Derivatives: Discovery of Receptor-Specific S-Enantiomers with Cytokinin or Anticytokinin Activities

“…Furthermore, the vast majority of natural monosaccharides belong to the D-configuration. At the same time, there are examples when L-isomers (L-Rha, L-Fuc, L-Ara) are the most common in nature; for example, L-Ara is more common in plants, while D-Ara is found in some species of microorganisms [ 36 , 37 , 38 ]. Chirality plays an extremely important role in most biochemical processes, because it affects the spatial arrangement of macromolecules and determines the convergence and interaction of active groups in enzyme–substrate complexes [ 37 , 39 , 40 ], which ensures the selectivity of biochemical processes occurring in the cell [ 41 ].…”