Chirality. 2026 Jun;38(6):e70107. doi: 10.1002/chir.70107.
ABSTRACT
The homochirality of life-the exclusive use of L-amino acids and the universal right-handedness of -helices-stands as one of the most persistent asymmetries in biology. While often attributed to kinetic or energetic biases, the overwhelming statistical dominance of these chiral forms still lacks a fully compelling thermodynamic and geometric explanation. Here, we propose a geometric mechanism for the stabilization and amplification of biomolecular handedness in open, entropy-producing systems. By introducing a local chirality marker based on the sign of a scalar triple product (equivalently, the sign of a determinant built from atomic coordinate differences and the local helical axis), we show that right-handed -helices can be can be represented as orientation-preserving sectors of the local configuration space in the local configuration space. Under physically admissible continuous backbone moves, chirality inversion requires crossing a degenerate subset where the marker vanishes, which constitutes a lower dimensional region of effectively zero measure in the feasible configuration manifold. Consequently, parity-inverting pathways are dynamically suppressed, and once a chiral sign becomes established, it tends to persist and amplify under irreversible evolution consistent with least-time free-energy dissipation. Our framework reframes biomolecular homochirality not as the consequence of a primordial energetic asymmetry but as an emergent, statistically stabilized standard arising from the interplay between nonequilibrium thermodynamics and the geometry of configuration space.
PMID:42204377 | DOI:10.1002/chir.70107
