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Fig 1.

Phylogenetic alignment performed with MEGA6.

The modified region is located in a highly conserved region among species.

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Fig 1 Expand

Fig 2.

(A) Pedigree chart of the family. (B) Chromatogram of the homozygous sequence variant c.109_126dup detected in the ARSA gene in the proband compared with the heterozygous sequence in the parents. The comparison of three sequences with the reference sequence is given at the bottom of the electropherograms. The red and yellow boxes indicate the duplicated and the previous sequences, respectively.

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Fig 2 Expand

Fig 3.

Conformational changes in ARSA proteins.

(A) all-atom RMSD, (B) RMSF and (C) Rg of WT-ARSA and mutant-ARSA.

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Fig 3 Expand

Table 1.

The average of various parameters during 100-ns MD simulation of wild type and mutant ARSAs.

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Table 1 Expand

Fig 4.

Graphical representation of solvent accessible surface area (SASA) of ARSA proteins.

(A) Total SASA and (B) active site SASA of WT-ARSA and mutant-ARSA.

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Fig 4 Expand

Fig 5.

The pattern of hydrogen bonds during 100 ns MD simulation for ARSA proteins.

(A) Intramolecular and (B) protein-solvent hydrogen bonds of WT-ARSA and mutant-ARSA.

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Fig 5 Expand

Fig 6.

Conformational sampling and Free energy landscape (FEL) analysis of ARSA proteins.

(A) Conformational sampling of WT-ARSA and mutant-ARSA proteins by 2D projection of the MD trajectory on PC1 and PC2. (B) FEL of WT-ARSA and (C) FEL of mutant-ARSA.

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Fig 6 Expand

Fig 7.

DNA sequences of Wilde Type ARSA and the mutated allele.

The 5′ one is shown in red (GACCTCGGC) and the 3′ one is shown in blue (GACCTGGGC). The underlined sequence is duplicated in the mutated allele.

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Fig 7 Expand