Foldseek-AlphaFold2#
In this tutorial, we introduce how TMKit can use a structural alignment method, Foldseek[1], for seeking functional similar protein structures to an input protein struture by searching a few databases.
Example usage#
First, a good scenario where Foldseek is applied is when we need to understand a predicted structure of a protein. For conveniences, we use 4 AlphaFold2-predicted structures of proteins P63092, Q9B6E8, P07256, and P63027. They are saved in ./data/.
import tmkit as tmk
import pandas as pd
prot_series = pd.Series(['P63092', 'Q9B6E8', 'P07256', 'P63027'])
tmk.seq.retrieve_pdb_alphafold(
prot_series=prot_series,
sv_fp='./data/',
)
Output#
===>No.1 protein name: P63092
======>successfully downloaded!
===>No.2 protein name: Q9B6E8
======>successfully downloaded!
===>No.3 protein name: P07256
======>successfully downloaded!
===>No.4 protein name: P63027
======>successfully downloaded!
Then, we can run tmk.seq.retrieve_foldseek to search a few databases by Foldseek. By default, the databases include afdb50, afdb-swissprot, afdb-proteome, cath50, mgnify_esm30, pdb100, and gmgcl_id. We can save the Foldseek results in ./data/ as well.
import tmkit as tmk
tmk.seq.retrieve_foldseek(
pdb_fp='./data/',
prot_name='P63027', # https://alphafold.ebi.ac.uk/entry/P63027
sv_fp='./data/',
)
Output#
===>Searching databases by foldseek...
===>Results have been saved!
Then, we can check the results using the following code. For example, we want to check the result for P63027 and the file is saved as ./data/P63027_foldseek_result.gz. Please find the output in section 3 Output below.
import tarfile
import pandas as pd
with tarfile.open('./data/P63027_foldseek_result.gz', "r") as tar:
csv_path = tar.getnames()[0]
for i in tar.getnames():
print(tar.extractfile(i))
df = pd.read_csv(tar.extractfile(i), header=None, sep="\t")
print(df)
Output#
===>Database: alis_afdb-proteome.m8
0 ... 20
0 job.pdb ... Rattus norvegicus
1 job.pdb ... Danio rerio
2 job.pdb ... Mus musculus
3 job.pdb ... Trichuris trichiura
4 job.pdb ... Cladophialophora carrionii
5 job.pdb ... Madurella mycetomatis
6 job.pdb ... Sporothrix schenckii ATCC 58251
7 job.pdb ... Schizosaccharomyces pombe 972h-
8 job.pdb ... Fonsecaea pedrosoi CBS 271.37
9 job.pdb ... Caenorhabditis elegans
10 job.pdb ... Histoplasma capsulatum G186AR
11 job.pdb ... Zea mays
[12 rows x 21 columns]
===>Database: alis_afdb-swissprot.m8
0 ... 20
0 job.pdb ... Homo sapiens
1 job.pdb ... Macaca mulatta
2 job.pdb ... Bos taurus
3 job.pdb ... Rattus norvegicus
4 job.pdb ... Mus musculus
5 job.pdb ... Xenopus laevis
6 job.pdb ... Mus musculus
7 job.pdb ... Bos taurus
8 job.pdb ... Homo sapiens
9 job.pdb ... Rattus norvegicus
10 job.pdb ... Mus musculus
11 job.pdb ... Macaca fascicularis
12 job.pdb ... Homo sapiens
13 job.pdb ... Caenorhabditis elegans
14 job.pdb ... Schistosoma mansoni
15 job.pdb ... Bos taurus
16 job.pdb ... Pongo abelii
17 job.pdb ... Saccharomyces cerevisiae S288C
18 job.pdb ... Schizosaccharomyces pombe 972h-
19 job.pdb ... Caenorhabditis elegans
20 job.pdb ... Homo sapiens
21 job.pdb ... Homo sapiens
[22 rows x 21 columns]
===>Database: alis_afdb50.m8
0 ... 20
0 job.pdb ... Danio rerio
1 job.pdb ... Danio rerio
2 job.pdb ... Mus musculus
3 job.pdb ... Macaca fascicularis
4 job.pdb ... Periophthalmus magnuspinnatus
.. ... ... ...
56 job.pdb ... Verrucomicrobia bacterium
57 job.pdb ... Caulobacter sp. FWC2
58 job.pdb ... Fusarium euwallaceae
59 job.pdb ... Jatropha curcas
60 job.pdb ... Tribolium castaneum
[61 rows x 21 columns]
===>Database: alis_cath50.m8
0 1 ... 19 20
0 job.pdb 3hd7A00 ... 10116 Rattus norvegicus
1 job.pdb 3hd7E00 ... 10116 Rattus norvegicus
2 job.pdb 1sfcE00 ... 10116 Rattus norvegicus
3 job.pdb 1sfcI00 ... 10116 Rattus norvegicus
4 job.pdb 1sfcA00 ... 10116 Rattus norvegicus
5 job.pdb 1kilA00 ... 9606 Homo sapiens
6 job.pdb 2n1tA00 ... 9606 Homo sapiens
7 job.pdb 5ccgG00 ... 10116 Rattus norvegicus
8 job.pdb 5ccgA00 ... 10116 Rattus norvegicus
9 job.pdb 5kj7A00 ... 10116 Rattus norvegicus
10 job.pdb 5cchA00 ... 10116 Rattus norvegicus
11 job.pdb 6ip1A00 ... 9913 Bos taurus
12 job.pdb 1l4aA00 ... 1051067 Doryteuthis pealeii
13 job.pdb 2npsA00 ... 10116 Rattus norvegicus
14 job.pdb 4wy4A00 ... 9606 Homo sapiens
15 job.pdb 3b5nA00 ... 559292 Saccharomyces cerevisiae S288C
[16 rows x 21 columns]
===>Database: alis_gmgcl_id.m8
0 ... 18
0 job.pdb ... YEVTNVSPDEITGDGPGFTDTEWDGDDVTASLPNPSEADDAAGVLD...
1 job.pdb ... LTTVSDEWCVSTCAAGCPPAASLWCRCEDVRAADAVPANQGAAAWG...
2 job.pdb ... IILSISNKQDTEKIQRESWNIWGTSQWYSTYTIMIKTDVDEYKIVE...
[3 rows x 19 columns]
===>Database: alis_mgnify_esm30.m8
0 ... 18
0 job.pdb ... MSIKYLLIGNPEDCEEIGHYPDRGASKTTAKEADKIFKKLSQSGIQ...
1 job.pdb ... MSIQYVLIGNPEDCEEIGHYPDRGASKSIAKEANQIFKKLSESGIK...
2 job.pdb ... MTSSSPYEYSAVARNTTILAQFANSNGNFDVLVTEILQKINIPENQ...
3 job.pdb ... MAVQYSSIYQGQDLLASKSNGSLPNNVKKLMDSIAIQAKPNDLACV...
4 job.pdb ... MASSSATTPACPSLRHVLIVRHDAAIREGTLLCEAWAAAVGTARTS...
5 job.pdb ... YLASDKTTGADVAIKEFFPRDYCGRAPDGSLAMSPGHNAGLVDTLK...
6 job.pdb ... LMFADGPLTQPPNLAALVRLAGTTAAVDRAIRLTEQQAGNLITTAA...
7 job.pdb ... MQEILPARGLARRRSLAASTGIGETTEMDQDSNQTSPGAVAAGPGS...
8 job.pdb ... APAASTAPAAPSGGPASACGPEAQGTTPEGRAERELLGALRARRAE...
[9 rows x 19 columns]
===>Database: alis_pdb100.m8
0 ... 20
0 job.pdb ... Rattus norvegicus
1 job.pdb ... Rattus norvegicus
[2 rows x 21 columns]
Results from each database contains 20 columns. Please see this issue comment for their explanations.
[
'job_desc',
'query','target','pident','alnlen','mismatch','gapopen','qstart','qend','tstart','tend','evalue','bits',
'qlen','tlen','qaln','taln','tca','tseq',
'taxid','taxname',
]