---
# System prepended metadata

title: Bioinformactics Project

---

In this project, I would like to explore the Parkinson's Disease. There is multiple proteins linked to the desease, the most notable would be Alpha-synuclein. The abnormal clumping of alpha-synuclein is the cause of the Parkinson's Disease.

We can find structure in the PDB with ID 1XQ8 and 6L1U. Its Uniprot ID is P37840

Its Sequence is 
```
MDVFMKGLSKAKEGVVAAAEKTKQGVAEAAGKTKEGVLYVGSKTKEGVVHGVAT
VAEKTKEQVTNVGGAVVTGVTAVAQKTVEGAGSIAAATGFVKKDQLGKNEEGAP
QEGILEDMPVDPDNEAYEMPSEEGYQDYEPEA
```

We can conduct a BLAST search with different species
    ![image](https://hackmd.io/_uploads/H1_mC_vx1x.png)
    
Then we can conduct a MSA
 CLUSTAL O(1.2.4) multiple sequence alignment

```
XP_037019156.1      MDVLMKGLSKAKEGVVAAAEKTKQGVAEAAGKTKEGVLYVGSKTKEGVVHGVTTVAEKTK	60
XP_024430550.1      MDVLMKGLSKAKEGVVAAAEKTKQGVAEAAGKTKEGVLYVGSKTKEGVVHGVTTVAEKTK	60
XP_021515032.1      MDVFMKGLSKAKEGVVAAAEKTKQGVAEAAGKTKEGVLYVGSKTKEGVVHGVTTVAEKTK	60
GAB1290881.1        MDVFMKGLSKAKEGVVAAAEKTKQGVAEAAGKTKEGVLYVGSKTKEGVVHGVTTVAEKTK	60
XP_012629476.1      MDIFKKGLSKAKEGVVAAAEKTKQGVAEAAGKTKEGVLYVGSKTKEGVVHGVTTVAEKTK	60
XP_045392790.1      MDIFKKGLSKAKEGVVAAAEKTKQGVAEAAGKTKEGVLYVGSKTKEGVVHGVTTVAEKTK	60
XP_066135802.1      MDVFMKGLSKAKEGVVAAAEKTKQSVTEAAGKTKEGVLYVGSKTKEGVVHGVTTVAEKTK	60
AAC00521.1          MDVFMKGLSKAKEGVVAAAEKTKQGVAEAAGKTKEGVLYVGSKTKEGVVHGVTTVAETTK	60
NP_001029213.1      MDVFMKGLSKAKEGVVAAAEKTKQGVAEAAGRTKEGVLYVGSKTKEGVVHGVTTVAEKTK	60
XP_055468768.1      MDVFMKGLSKAKEGVVAAAEKTRQGVAEAAGKTKEGVLYVGSKTKEGVVQGVTTVAEKTK	60
KAK2105827.1        MDVFMKVLSKAREGVVAAAEKTKQGVAEAAGKTKEGVLYVGSKTKEGVAHGVTTVAEKTK	60
KAI2535189.1        MDVFMKGLSKAKEGVVAAAEKTKQGVAEAAGKTKEGVLYVGSKTKEGVVHGVATVAEKTK	60
                    **:: * ****:**********:*.*:****:****************.:**:****.**

XP_037019156.1      EQVTNVGEAVVTGVTAVAQKTVEGAGNIAAATGFGKKDQLGKS-----------------	103
XP_024430550.1      EQVTNVGEAVVTGVTAVAQKTVEGAGNIAAATGFGRKDQLGKS-----------------	103
XP_021515032.1      EQVTNVGGAVVTGVTAVAQKTVEGAGNIAAATGFVKKDQMGKG-----------------	103
GAB1290881.1        EQVTNVGGAVVTGVTAVAQKTVEGAGNIAAATGFVKKDQMGKG-----------------	103
XP_012629476.1      EQVTNVGGAVVTGVTAVAQKTVEGAGSIAAATGFGKKDQFGKS-----------------	103
XP_045392790.1      EQVTNVGGAVVTGVTAVAQKTVEGAGSIAAATGFGKKDQFGKS-----------------	103
XP_066135802.1      EQVTNVGEAVVTGVTAVAQKTVEGAGNIAAATGFGKKDQLGKS-----------------	103
AAC00521.1          EQVTNVGGAVVTGVTAVAQKTVEGAGNIAAATGFVKKDQMGKG-----------------	103
NP_001029213.1      EQVTNVGEAVVTGVTAVAQKTVEGAGSIAAATGFGKKDHMGKG-----------------	103
XP_055468768.1      EQVTNVGGAVVTGVTAVAQKTVEGAGNIAAATGFVKKDQMGKG-----------------	103
KAK2105827.1        EQVTNVGGAVVTGVTAVAQKTVEGAGNIAAATGFVKKDHLGKS-----------------	103
KAI2535189.1        EQVTNVGGAVVTGVTAVAQKTVEGAGSIAAATGFVKKDQLGKSSLRNECSPEPAASTDQS	120
                    ******* ******************.******* :**::**.                 

XP_037019156.1      --EEGAPQEGILEDMPGDPDNETYEMPSEEGYQDYEPEA	140
XP_024430550.1      --EEGAPQEGILEDMPGDPDNETYEMPSEEGYQDYEPEA	140
XP_021515032.1      --EEGYPQEGILEDMPVDPGSEAYEMPSEEGYQDYEPES	140
GAB1290881.1        --EEGYPQEGILEDMPVDPGSEAYEMPAEEGYQDYEPEA	140
XP_012629476.1      --EEGAPQEGILEDSPMDPDSEAYEMPSEEGYQDYEPEA	140
XP_045392790.1      --EEGAPQEGILEDTPVDPDSEAYEMPSEEGYQDYEPEA	140
XP_066135802.1      --EEGAPQEGILEDMPGDPDNETYEMPSEEGYQDYEPEA	140
AAC00521.1          --EEGYPQEGILEDMPVDPGSEAYEMPSEEGYQDYEPEA	140
NP_001029213.1      --EEGASQEGILEDMPVDPDNEAYEMPSEEGYQDYEPEA	140
XP_055468768.1      --EEGYPQEGILEDMPVDPGSEAYEMPSEEGYQDYEPES	140
KAK2105827.1        --EEGAPREGILEDMLVDPDNEAYEMPSEEGYQDYEPEA	140
KAI2535189.1        QNEEGAPQEGILEDMPVDPDNEAYEMPSEEGYQDYEPEA	159
                      ***  :******   **..*:****:**********:
```
From the Weblogo, we can see it is highly similar

![image](https://hackmd.io/_uploads/SJRFpOPgke.png)

We can also found a normal Alpha-synuclein
![image](https://hackmd.io/_uploads/ryQQK4YLJg.png)
as well as the abnormal Alpha-synuclein
![image](https://hackmd.io/_uploads/HkWZYEYU1e.png)

We can note that normally the protein should adots an alpha-helical conformation but the abnormal ony misfold into a beta-sheet structures.

![image](https://hackmd.io/_uploads/r1vm94KUkx.png)

We can also see the result from KEGG and STRING to analyse the pathway of Alpha-synuclein (SNCA) and the Parkinson's Diesease.
![image](https://hackmd.io/_uploads/BkIacNFIkg.png)
![image](https://hackmd.io/_uploads/HkwA54FU1e.png)

A quick screening of drug is done using iGEMDock v2.1

![image](https://hackmd.io/_uploads/HkaIi4FU1l.png)
![image](https://hackmd.io/_uploads/B1Auo4tLyx.png)


One of the best docked result is shown as follow in Pymol:
![image](https://hackmd.io/_uploads/SkFytVKIkl.png)
