Furthermore, compared to the WTPrP106-126, the A117V mutant is also more inclined to sample ��-bridge structure which is considered to be prelude to the formation of ��-sheet, especially for the residues Lys110 and Val117. On the contrary, the H111S mutation displays weaker tendency to acquire ��-bridge structure. On the whole, the A117V and H111S mutations induce the significant changes in secondary structures of PrP106-126. The A117V mutant has an increased probability to acquire ��-structure while the H111S mutation can increase the probability to form helical structure. Our extensive REMD simulations show that the monomeric A117V mutated PrP106-126 exhibits the higher contents of ��-hairpin in contrast with its wildtype, consistent with the results of MonteCarlo simulations. The CD spectroscopy experiments suggested that the A117V mutation increased ��-sheet structure. Based on the helix propensity scale proposed by Pace and Scholtz, serine occurs more frequently in helices than histidine. Therefore, it can be deduced that the H111S mutation may enhance the helix propensity of PrP106-126. Previous experimental so shed light on the effects of H111S on the secondary structures of PrP106-126. It has been suggested that the H111S mutation does not alter the secondary structure of the peptide. This inconsistency also can be Paromomycin Sulfate attributed to different treatments of terminal amino acids. In the experiments, the H111S mutated peptide was not capped, while the terminal amino acids were both blocked in our study. Furthermore, it has been observed that the terminal blocked PrP106-126 is more helical in this experiment. Herein, it is reasonable that the blocked H111S mutated PrP106-126 may present enhanced tendency to adopt helical configurations than its uncapped analogue. To obtain an overall view of conformational distributions of the WTPrP106-126 and its two mutants A117V and H111S, two-dimensional free energy and scapes of the three species were Tenatoprazole constructed using Rg and end-to-end distance as reaction coordinates. As Fig 5 shows, for each system, the global energy landscape is similar to each other.