In contrast with the 117th residue in the WTPrP106-126, the residue Val117 in the A117V mutant exhibits weaker tendency to contact with other residues. However, the propensity of this residue to form hydrogen bond is similar to WT. Moreover, the inclusion of Val117 enhances the hydrogen bond formation propensity of its neighbor residues Ala116 and Ala118. The increased frequency of hydrogen bond formation of these residues may indicate that the large hydrophobic side chain of Val117 may be tend to stick out and be solvated, which can spare space for backbone interaction and facilitate hydrogen bond formation. The exposure of hydrophobic Val117 also may increase its propensity to interact with the side chains of the other monomers, which may accelerate the aggregation of PrP106-126. To validate this assumption, the average solvent accessible surface areas of the side chain of the 117th residue were calculated in 40�C200ns time interval. The calculated values for A117 in WTPrP106-126 and V117 in A117V mutant are 87 and 137?2, respectively, indicating that the 117th residue tends to be exposed in A117V mutant. Because hydrophobic interactions play considerable role in the aggregation of PrP106-126, the exposed Val117 may serve as hot spot to drive the aggregation. Daidone et al. also have proposed the notion that the side chain of Val117 in A117V mutated PrP109-122 remains exposed to the solvent. Furthermore, the MD simulations of oligomers performed by this group have suggested that the side chains of Val117become involved in the formation of hydrophobic cores, which agrees with our assumption that Val117 may be the hotspot in oligomer formation. The Sodium ascorbate overall hydrophobic SASA of the three peptides were also calculated and their distributions were compared. As shown in Fig 10, the A117V mutated PrP106-126 has larger hydrophobic surface areas, with the shift of SASA distributions toward larger values relative to the WT and H111S. Previous computational studies have proved that pathogenic Tamibarotene mutations in prion protein suchas V210I, T183A, V180I, F198S, T188K/R/A increase the SASA of hydrophobic residues.