Tacticity-Driven Intrachain Hydrogen-Bond Selection Encodes Single-Chain Conformational Metastability in Water

The capacity of a single chain to populate multiple metastable conformations governs molecular memory and function in systems as diverse as folded proteins, intrinsically disordered regions, and single-chain nanoparticles. In all of these, such conformational diversity is built from evolved sequence heterogeneity or purpose-designed recognition units, leaving open whether a simpler, intrinsic molecular variable can encode it in water. Using all-atom molecular dynamics simulations of isotactic, atactic, and syndiotactic poly(1,3-propanediol) (P3) and poly(vinyl alcohol) (PVA) as single chains in explicit water (CGenFF/TIP3P, 298 K), we show that backbone stereochemistry alone geometrically selects the intrachain hydrogen-bond (IHB) motif: isotactic P3 forms 1-3 IHBs, syndiotactic P3 favors 1-4 IHBs, and PVA suppresses 1-4 IHBs at every tacticity. Because backbone torsion-angle distributions are nearly identical across all six systems, these IHBs, not backbone rigidity, are the primary conformational driver. Syndiotactic P3 alone develops three thermally interconverting metastable states separated by barriers comparable to the thermal energy k_BT: a compact spiral, a loosely coiled, and an extended rod conformation. Conformational diversity grows from isotactic to syndiotactic P3, whereas PVA remains unimodal at every tacticity, identifying abundant 1-4 IHBs as a necessary condition for metastability. Strikingly, the three states carry nearly identical numbers of 1-4 IHBs, yet their identity is set instead by the directional alignment of those IHBs along the chain. Backbone stereochemistry thus emerges as a minimal molecular principle for encoding single-chain conformational metastability in water, requiring neither chemical sequence nor designed interactions.