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The neurofibrillary tangles(NFTs)formed by Tau proteins inside neurons arecharacterized as the pathological hallmark of a series of neurodegenerative diseases namedtauopathies,including the Alzheimer's disease(AD).However,the transition of Tau fromintrinsically disordered soluble proteins with normal biological function to insoluble cytotoxicaggregates remains mostly unclear.Recently,Tau proteins were discovered to undergoliquid-liquid phase separation(LLPS)both in solution and cells,the resulting droplet formationacts as the initial step toward aberrant Tau aggregation1-2.The liquid-liquid phase separation ofTau proteins is complicated,depending on various environmental factors,such as temperature,ionic strength,and phosphorylation of the protein itself.Here,we performed all-atom replicaexchange molecular dynamics(REMD)simulations on two truncated Tau constructs,K18 andK19,providing insights into relationships between monomeric conformations and liquid-liquidphase separation of Tau.Our simulations show that structures of K18 and K19 monomers aresensitive to temperature changes.The radius of gyration(Rg)of K18 and K19 monomersdecreases as heating to around 350 K,whereas it starts to increase when the temperature continuesto rise.The probabilities of ordered secondary structures exhibit opposite dependency totemperatures as compared to Rg: K18 and K19 monomers adopt higher propensity of β and helix structures around 330~370 K,with their structures becoming less ordered at both lower and highertemperatures.The solvent accessible surface area(SASA)of K18 and K19 also varies withtemperatures,especially the two critical hexapeptides 275VQIINK280 in R2 and 306VQIVYK311 inR3,which are crucial for Tau aggregation.The structural characteristics of K18 and K19monomers display similar temperature dependence and sensitivity as compared to the liquid-liquidphase separation behavior of Tau,indicating that the ability of Tau proteins to phase separateencodes inside their monomer conformations.We propose that the relatively ordered and compactstructures adopted by K18 and K19 monomers in a certain temperature range are favorable for theliquid-liquid phase separation of Tau proteins.