The heterogeneity of the synucleinopathies, neurological disorders that include Parkinson's disease (PD), indicates that toxicity, seeding/cross-seeding ability, and propagation of alpha-synuclein (alpha S) assemblies depend on their distinct structural characteristics or "strain''. To examine the molecular signature that encodes the aggregation seed, conformational preference, and thermodynamic stability of full-length alpha S fibrils, we performed molecular dynamics simulations on two non-amyloid-beta component (NAC) fibril structures, containing residues 61-95 of two distinct alpha S fibrils. We identified several discrete hot spots in the recognized hydrophobic core of NAC (residues 68-82) that could initiate the early assembly of alpha S. We show that NAC fibrils inherit the preferred fold of their parent alpha S fibril, but could switch conformational preference in two fibril mutants K80Q and E83Q under different solution conditions. Similar to alpha S fibrils, NAC fibrils are also sensitive to temperature and salt concentration. The favorable solvation free energy of NAC fibrils at low temperature (280 K) suggests a propensity for cold-denaturation. Our results indicate that the strain-dependent synucleinopathies may be partially imprinted in the fold-dependent thermodynamic properties of NAC fibrils, providing structural insights into the emerging development of anti-PD treatments that target the NAC region of alpha S.