This notebook is the second in the training material series, and focuses on getting information for multiple PDB entries using the REST search API of PDBe.
First, we import some packages that we will use, and set some variables.
Note: Full list of valid URLs is available from https://www.ebi.ac.uk/pdbe/api/doc/
[1]:
import requests # used for getting data from a URL
from pprint import pprint # pretty print
import matplotlib.pyplot as plt # plotting results
import pandas as pd # used for turning results into mini databases
# make graphs show on the page
%matplotlib inline
# use plotly and cufflinks to make interactive plots
import cufflinks as cf
from plotly.offline import download_plotlyjs, init_notebook_mode, plot, iplot
init_notebook_mode(connected=True)
cf.go_offline()
# settings for PDBe API
base_url = "https://www.ebi.ac.uk/pdbe/" # the beginning of the URL for PDBe's API.
api_base = base_url + "api/"
search_url = base_url + 'search/pdb/select?' # the rest of the URL used for PDBe's search API.
Let’s start with defining a function that can be used to GET data from the PDBe search API.
[2]:
def make_request(search_term, number_of_rows=10):
"""
This function can make GET requests to
the PDBe search API
:param url: String,
:param pdb_id: String
:return: JSON
"""
search_variables = '&wt=json&rows={}'.format(number_of_rows)
url = search_url+search_term+search_variables
print(url)
response = requests.get(url)
if response.status_code == 200:
return response.json()
else:
print("[No data retrieved - %s] %s" % (response.status_code, response.text))
return {}
This will allow us to use human readable search terms and this function will make a URL that the search API can handle.
[3]:
def format_search_terms(search_terms, filter_terms=None):
# print('formatting search terms: %s' % search_terms)
search_string = ''
filter_string = ''
search_list = []
if isinstance(search_terms, dict):
for key in search_terms:
term = search_terms.get(key)
if ' ' in term:
if not '"' in term:
term = '"{}"'.format(term)
elif not "'" in term:
term = "'{}'".format(term)
search_list.append('{}:{}'.format(key, term))
search_string = ' AND '.join(search_list)
else:
if '&' in search_terms:
search_string = search_terms.replace('&', ' AND ')
else:
search_string = search_terms
if filter_terms:
filter_string = '&fl={}'.format(','.join(filter_terms))
# print('formatted search terms: %s' % search_string)
final_search_string = 'q={}{}'.format(search_string, filter_string)
return final_search_string
This function will run the search and will return a list of the results
[4]:
def run_search(search_terms, filter_terms=None, number_of_rows=100):
search_term = format_search_terms(search_terms, filter_terms)
response = make_request(search_term, number_of_rows)
results = response.get('response', {}).get('docs', [])
print('Number of results for {}: {}'.format(','.join(search_terms.values()), len(results)))
return results
Now we are ready to actually run a search against the PDB API for entries containing human Dihydrofolate reductase in the PDB. This will return a list of results - only 10 to start with.
A list of search terms is available at: https://www.ebi.ac.uk/pdbe/api/doc/search.html
This will return details of human Dihydrofolate reductase’s in the PDB
The search terms are defined as a dictionary (a hash in other programming lanuguages). e.g. {“molecule_name”:“Dihydrofolate reductase”} Here we are searching for molecules named Dihydrofolate reductase. If we search for two terms i.e. molecule_name and organism_scientific_name then we will get molecules that match both search terms.
We will return the number of results for two searches.
The first one will hit the limit of 100. There are more than 100 Dihydrofolate reductase structures. We have to add the argument “number_of_rows” to a higher number, say 1000, to find all the examples.
[5]:
print('1st search')
search_terms = {"molecule_name":"Dihydrofolate reductase"}
results = run_search(search_terms)
1st search
https://www.ebi.ac.uk/pdbe/search/pdb/select?q=molecule_name:"Dihydrofolate reductase"&wt=json&rows=100
Number of results for Dihydrofolate reductase: 100
[6]:
results = run_search(search_terms, number_of_rows=1000)
https://www.ebi.ac.uk/pdbe/search/pdb/select?q=molecule_name:"Dihydrofolate reductase"&wt=json&rows=1000
Number of results for Dihydrofolate reductase: 365
We will add organism_name of Human to the query to limit the results to only return those that are structures of Human Dihydrofolate reductase.
[7]:
print('2nd search')
search_terms = {"molecule_name":"Dihydrofolate reductase",
"organism_name":"Human"
}
results = run_search(search_terms)
2nd search
https://www.ebi.ac.uk/pdbe/search/pdb/select?q=molecule_name:"Dihydrofolate reductase" AND organism_name:Human&wt=json&rows=100
Number of results for Dihydrofolate reductase,Human: 79
We will then look at the last result. We will print the data we have for the first result.
This will be the first item of the list “results” i.e. results[0]
We are using “pprint” (pretty print) rather than “print” to make the result easier to read.
[8]:
pprint(results[0])
{'_version_': 1656713747957284864,
'abstracttext_unassigned': ['The synthesis and biological activities of 14 '
'6-substituted 2,4-diaminoquinazolines are '
'reported. These compounds were designed to '
'improve the cell penetration of a previously '
'reported series of '
'2,4-diamino-6-substituted-pyrido[2,3-d]pyrimidines '
'which had shown significant potency and '
'remarkable selectivity for Toxoplasma gondii '
'dihydrofolate reductase (DHFR), but had much '
'lower inhibitory effects on the growth of T. '
'gondii cells in culture. The target N9-H '
'analogues were obtained via regiospecific '
'reductive amination of the appropriate '
'benzaldehydes with 2,4,6-triaminoquinazoline, '
'which, in turn, was synthesized from '
'2,4-diamino-6-nitroquinazoline. The N9-CH3 '
'analogues were synthesized via a regiospecific '
'reductive methylation of the corresponding N9-H '
'precursors. The compounds were evaluated as '
'inhibitors of DHFR from human, Pneumocystis '
'carinii, T. gondii, rat liver, Lactobacillus '
'casei, and Escherichia coli, and selected '
'analogues were evaluated as inhibitors of the '
'growth of tumor cells in culture. These '
'analogues displayed potent T. gondii DHFR '
'inhibition as well as inhibition of the growth '
'of T. gondii cells in culture. Further, selected '
'analogues were potent inhibitors of the growth '
'of tumor cells in culture in the in vitro '
'screening program of the National Cancer '
'Institute with GI50s in the nanomolar and '
'subnanomolar range. Crystallographic data for '
'the ternary complex of hDHFR-NADPH and '
"2,4-diamino-6-[N-(2', "
"5'-dimethoxybenzyl)-N-methylamino]pyrido[2,3-d]pyrimidine, "
'1c, reveal the first structural details for a '
'reversed N9-C10 folate bridge geometry as well '
'as the first conformational details of a hybrid '
'piritrexim-trimetrexate analogue.'],
'all_assembly_composition': ['protein structure'],
'all_assembly_form': ['homo'],
'all_assembly_id': ['1'],
'all_assembly_mol_wt': [22.363],
'all_assembly_type': ['monomer'],
'all_authors': ['Cody V',
'Galitsky N',
'Gangjee A',
'Kisliuk RL',
'Li R',
'Luft JR',
'Pangborn W',
'Queener SF',
'Vasudevan A',
'Vidwans AP'],
'all_compound_names': ['PRD : '
'N6-(2,5-DIMETHOXY-BENZYL)-N6-METHYL-PYRIDO[2,3-D]PYRIMIDINE-2,4,6-TRIAMINE',
'NDP : NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE '
'PHOSPHATE',
'PRD : '
'N~6~-(2,5-dimethoxybenzyl)-N~6~-methylpyrido[2,3-d]pyrimidine-2,4,6-triamine',
'PRD : '
'N6-[(2,5-dimethoxyphenyl)methyl]-N6-methyl-pyrido[5,6-e]pyrimidine-2,4,6-triamine',
'NDP : '
'[[(2R,3S,4R,5R)-5-(3-aminocarbonyl-4H-pyridin-1-yl)-3,4-dihydroxy-oxolan-2-yl]methoxy-hydroxy-phosphoryl] '
'[(2R,3R,4R,5R)-5-(6-aminopurin-9-yl)-3-hydroxy-4-phosphonooxy-oxolan-2-yl]methyl '
'hydrogen phosphate'],
'all_enzyme_names': ['Oxidoreductases',
'Acting on the CH-NH group of donors',
'With NAD(+) or NADP(+) as acceptor',
'Dihydrofolate reductase',
'1.5.1.3 : Dihydrofolate reductase',
'5,6,7,8-tetrahydrofolate:NADP(+) oxidoreductase'],
'all_go_terms': ['cytoplasm',
'mitochondrion',
'cytosol',
'folic acid binding',
'oxidoreductase activity',
'NADPH binding',
'sequence-specific mRNA binding',
'RNA binding',
'mRNA binding',
'NADP binding',
'methotrexate binding',
'dihydrofolate reductase activity',
'translation repressor activity, mRNA regulatory element '
'binding',
'drug binding',
'one-carbon metabolic process',
'negative regulation of translation',
'folic acid metabolic process',
'response to methotrexate',
'regulation of removal of superoxide radicals',
'tetrahydrofolate metabolic process',
'tetrahydrobiopterin biosynthetic process',
'tetrahydrofolate biosynthetic process',
'positive regulation of nitric-oxide synthase activity',
'regulation of transcription involved in G1/S transition of '
'mitotic cell cycle',
'oxidation-reduction process',
'axon regeneration',
'dihydrofolate metabolic process'],
'all_molecule_names': ['Dihydrofolate reductase', 'Dihydrofolate reductase'],
'all_num_interacting_entity_id': [0],
'all_sequence_family': ['IPR001796 : Dihydrofolate reductase domain',
'IPR024072 : Dihydrofolate reductase-like domain '
'superfamily',
'PF00186 : DHFR_1',
'CL0387 : DHFred'],
'all_structure_family': ['3-Layer(aba) Sandwich',
'Alpha Beta',
'3.40.430.10',
'Dihydrofolate Reductase, subunit A',
'Dihydrofolate Reductase, subunit A',
'Alpha and beta proteins (a/b)',
'Dihydrofolate reductases',
'Dihydrofolate reductase-like',
'Dihydrofolate reductase-like'],
'assembly_composition': ['protein structure'],
'assembly_form': ['homo'],
'assembly_id': ['1'],
'assembly_mol_wt': 22.363,
'assembly_num_component': [1],
'assembly_type': ['monomer'],
'beam_source_name': ['Rotating anode'],
'biological_cell_component': ['cytoplasm', 'mitochondrion', 'cytosol'],
'biological_function': ['folic acid binding',
'oxidoreductase activity',
'NADPH binding',
'sequence-specific mRNA binding',
'RNA binding',
'mRNA binding',
'NADP binding',
'methotrexate binding',
'dihydrofolate reductase activity',
'translation repressor activity, mRNA regulatory '
'element binding',
'drug binding'],
'biological_process': ['one-carbon metabolic process',
'negative regulation of translation',
'folic acid metabolic process',
'response to methotrexate',
'regulation of removal of superoxide radicals',
'tetrahydrofolate metabolic process',
'tetrahydrobiopterin biosynthetic process',
'tetrahydrofolate biosynthetic process',
'positive regulation of nitric-oxide synthase activity',
'regulation of transcription involved in G1/S '
'transition of mitotic cell cycle',
'oxidation-reduction process',
'axon regeneration',
'dihydrofolate metabolic process'],
'bound_compound_id': ['PRD', 'NDP'],
'bound_compound_name': ['PRD : '
'N6-(2,5-DIMETHOXY-BENZYL)-N6-METHYL-PYRIDO[2,3-D]PYRIMIDINE-2,4,6-TRIAMINE',
'NDP : NADPH '
'DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE'],
'bound_compound_systematic_name': ['PRD : '
'N~6~-(2,5-dimethoxybenzyl)-N~6~-methylpyrido[2,3-d]pyrimidine-2,4,6-triamine',
'PRD : '
'N6-[(2,5-dimethoxyphenyl)methyl]-N6-methyl-pyrido[5,6-e]pyrimidine-2,4,6-triamine',
'NDP : '
'[[(2R,3S,4R,5R)-5-(3-aminocarbonyl-4H-pyridin-1-yl)-3,4-dihydroxy-oxolan-2-yl]methoxy-hydroxy-phosphoryl] '
'[(2R,3R,4R,5R)-5-(6-aminopurin-9-yl)-3-hydroxy-4-phosphonooxy-oxolan-2-yl]methyl '
'hydrogen phosphate'],
'bound_compound_weight': [340.38, 745.421],
'cath_architecture': ['3-Layer(aba) Sandwich'],
'cath_class': ['Alpha Beta'],
'cath_code': ['3.40.430.10'],
'cath_homologous_superfamily': ['Dihydrofolate Reductase, subunit A'],
'cath_topology': ['Dihydrofolate Reductase, subunit A'],
'cell_a': 86.259,
'cell_alpha': 90.0,
'cell_b': 86.259,
'cell_beta': 90.0,
'cell_c': 77.637,
'cell_gamma': 120.0,
'citation_authors': ['Gangjee A',
'Vidwans AP',
'Vasudevan A',
'Queener SF',
'Kisliuk RL',
'Cody V',
'Li R',
'Galitsky N',
'Luft JR',
'Pangborn W'],
'citation_doi': '10.1021/jm980081y',
'citation_title': 'Structure-based design and synthesis of lipophilic '
'2,4-diamino-6-substituted quinazolines and their '
'evaluation as inhibitors of dihydrofolate reductases and '
'potential antitumor agents.',
'citation_year': 1998,
'cofactor_class': ['Nicotinamide-adenine dinucleotide'],
'cofactor_id': ['NDP'],
'compound_id': ['PRD', 'NDP'],
'compound_name': ['PRD : '
'N6-(2,5-DIMETHOXY-BENZYL)-N6-METHYL-PYRIDO[2,3-D]PYRIMIDINE-2,4,6-TRIAMINE',
'NDP : NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE '
'PHOSPHATE'],
'compound_systematic_name': ['PRD : '
'N~6~-(2,5-dimethoxybenzyl)-N~6~-methylpyrido[2,3-d]pyrimidine-2,4,6-triamine',
'PRD : '
'N6-[(2,5-dimethoxyphenyl)methyl]-N6-methyl-pyrido[5,6-e]pyrimidine-2,4,6-triamine',
'NDP : '
'[[(2R,3S,4R,5R)-5-(3-aminocarbonyl-4H-pyridin-1-yl)-3,4-dihydroxy-oxolan-2-yl]methoxy-hydroxy-phosphoryl] '
'[(2R,3R,4R,5R)-5-(6-aminopurin-9-yl)-3-hydroxy-4-phosphonooxy-oxolan-2-yl]methyl '
'hydrogen phosphate'],
'compound_weight': [340.38, 745.421],
'crystallisation_cond': ['pH 6.5'],
'crystallisation_ph': [6.5],
'data_quality': -1.0,
'data_scaling_software': ['SCALEPACK'],
'deposition_date': '1998-08-06T01:00:00Z',
'deposition_site': 'BNL',
'deposition_year': 1998,
'detector': ['Image plate'],
'detector_type': ['RIGAKU RAXIS'],
'diffraction_protocol': ['Single wavelength'],
'diffraction_source_type': ['RIGAKU RU200'],
'diffraction_wavelengths': [1.5418],
'ec_hierarchy_name': ['Oxidoreductases',
'Acting on the CH-NH group of donors',
'With NAD(+) or NADP(+) as acceptor',
'Dihydrofolate reductase'],
'ec_number': ['1.5.1.3'],
'entity_id': 1,
'entity_weight': 21259.402,
'entry_author_list': ['Gangjee A, Vidwans AP, Vasudevan A, Queener SF, '
'Kisliuk RL, Cody V, Li R, Galitsky N, Luft JR, '
'Pangborn W'],
'entry_authors': ['Gangjee A',
'Vidwans AP',
'Vasudevan A',
'Queener SF',
'Kisliuk RL',
'Cody V',
'Li R',
'Galitsky N',
'Luft JR',
'Pangborn W'],
'entry_entity': '1boz_1',
'entry_lig_entity': ['1boz_PRD_3', '1boz_NDP_2'],
'entry_organism_scientific_name': ['Homo sapiens|9606'],
'enzyme_name': ['Dihydrofolate reductase'],
'enzyme_num_name': ['1.5.1.3 : Dihydrofolate reductase'],
'enzyme_systematic_name': ['5,6,7,8-tetrahydrofolate:NADP(+) oxidoreductase'],
'experimental_method': ['X-ray diffraction'],
'gene_name': ['DHFR'],
'genus': ['Homo'],
'go_id': ['GO:0006730',
'GO:0017148',
'GO:0046655',
'GO:0031427',
'GO:2000121',
'GO:0046653',
'GO:0006729',
'GO:0046654',
'GO:0051000',
'GO:0000083',
'GO:0055114',
'GO:0031103',
'GO:0046452',
'GO:0005542',
'GO:0016491',
'GO:0070402',
'GO:1990825',
'GO:0003723',
'GO:0003729',
'GO:0050661',
'GO:0051870',
'GO:0004146',
'GO:0000900',
'GO:0008144',
'GO:0005737',
'GO:0005739',
'GO:0005829'],
'go_mapping': ['GO:0006730 : one-carbon metabolic process',
'GO:0017148 : negative regulation of translation',
'GO:0046655 : folic acid metabolic process',
'GO:0031427 : response to methotrexate',
'GO:2000121 : regulation of removal of superoxide radicals',
'GO:0046653 : tetrahydrofolate metabolic process',
'GO:0006729 : tetrahydrobiopterin biosynthetic process',
'GO:0046654 : tetrahydrofolate biosynthetic process',
'GO:0051000 : positive regulation of nitric-oxide synthase '
'activity',
'GO:0000083 : regulation of transcription involved in G1/S '
'transition of mitotic cell cycle',
'GO:0055114 : oxidation-reduction process',
'GO:0031103 : axon regeneration',
'GO:0046452 : dihydrofolate metabolic process',
'GO:0005542 : folic acid binding',
'GO:0016491 : oxidoreductase activity',
'GO:0070402 : NADPH binding',
'GO:1990825 : sequence-specific mRNA binding',
'GO:0003723 : RNA binding',
'GO:0003729 : mRNA binding',
'GO:0050661 : NADP binding',
'GO:0051870 : methotrexate binding',
'GO:0004146 : dihydrofolate reductase activity',
'GO:0000900 : translation repressor activity, mRNA regulatory '
'element binding',
'GO:0008144 : drug binding',
'GO:0005737 : cytoplasm',
'GO:0005739 : mitochondrion',
'GO:0005829 : cytosol'],
'has_bound_molecule': 'Y',
'has_modified_residues': 'N',
'homologus_pdb_entity_id': ['4qhv_1',
'6dav_1',
'1dlr_1',
'4kak_1',
'4keb_1',
'5hqy_1',
'5hqz_1',
'1u72_1',
'2w3b_1',
'5hsr_1',
'5ht4_1',
'3nu0_1',
'3nxo_1',
'3nxt_1',
'3nxv_1',
'2c2s_1',
'3nxr_1',
'1hfr_1',
'1s3v_1',
'1s3w_1',
'1u71_1',
'1yho_1',
'2w3a_1',
'3nxy_1',
'3nzd_1',
'3s7a_1',
'5hve_1',
'1dls_1',
'1drf_1',
'1mvs_1',
'2c2t_1',
'4m6j_1',
'1kms_1',
'1pd9_1',
'3ghc_1',
'3ghw_1',
'3ntz_1',
'3nxx_1',
'1pdb_1',
'3f8y_1',
'3gi2_1',
'6a7e_1',
'1pd8_1',
'4ddr_1',
'4m6k_1',
'3f8z_1',
'3f91_1',
'3fs6_1',
'4m6l_1',
'4qjc_1',
'5hsu_1',
'1boz_1',
'3n0h_1',
'4kfj_1',
'1kmv_1',
'1mvt_1',
'3oaf_1',
'4kd7_1',
'5hpb_1',
'6a7c_1',
'1ohj_1',
'3gyf_1',
'4g95_1',
'5hui_1',
'1dhf_1',
'1s3u_1',
'2dhf_1',
'3ghv_1',
'1hfp_1',
'1hfq_1',
'1ohk_1',
'2w3m_1',
'3eig_1',
'3l3r_1',
'3s3v_1',
'4kbn_1',
'5ht5_1',
'5hvb_1',
'6de4_1'],
'interacting_ligands': ['PRD : '
'N6-(2,5-DIMETHOXY-BENZYL)-N6-METHYL-PYRIDO[2,3-D]PYRIMIDINE-2,4,6-TRIAMINE',
'NDP : NADPH '
'DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE'],
'interpro': ['IPR001796 : Dihydrofolate reductase domain',
'IPR024072 : Dihydrofolate reductase-like domain superfamily'],
'interpro_accession': ['IPR001796', 'IPR024072'],
'interpro_name': ['Dihydrofolate reductase domain',
'Dihydrofolate reductase-like domain superfamily'],
'inv_overall_quality': 173.0,
'journal': 'J. Med. Chem.',
'journal_page': '3426-34',
'journal_volume': '41',
'matthews_coefficient': 2.61,
'max_observed_residues': 186,
'mesh_terms': 'Animals,Antineoplastic Agents,Cell Division,Crystallography, '
'X-Ray,Drug Design,Drug Screening Assays, Antitumor,Escherichia '
'coli,Folic Acid Antagonists,Humans,Liver,Models, '
'Molecular,Molecular '
'Structure,NADP,Pneumocystis,Pyridines,Pyrimidines,Quinazolines,Rats,Structure-Activity '
'Relationship,Tetrahydrofolate Dehydrogenase,Toxoplasma,Tumor '
'Cells, Cultured',
'model_quality': 16.12,
'modified_residue_flag': 'N',
'molecule_name': ['Dihydrofolate reductase'],
'molecule_sequence': 'VGSLNCIVAVSQNMGIGKNGDLPWPPLRNEGRYFQRMTTTSSVEGKQNLVIMGKKTWFSIPEKNRPLKGRINLVLSRELKEPPQGAHFLSRSLDDALKLTEQPELANKVDMVWIVGGSSVYKEAMNHPGHLKLFVTRIMQDFESDTFFPEIDLEKYKLLPEYPGVLSDVQEEKGIKYKFEVYEKND',
'molecule_synonym': ['Dihydrofolate reductase'],
'molecule_type': 'Protein',
'mutation': 'y',
'mutation_info': ['F31G'],
'mutation_type': ['Conflict'],
'nigli_cell_a': 56.124,
'nigli_cell_alpha': 100.433,
'nigli_cell_b': 56.124,
'nigli_cell_beta': 100.433,
'nigli_cell_c': 56.124,
'nigli_cell_gamma': 100.433,
'nigli_cell_symmetry': 'R32',
'num_interacting_entity_id': [0],
'number_of_bound_entities': 2,
'number_of_bound_molecules': 2,
'number_of_copies': 1,
'number_of_models': 1,
'number_of_polymer_entities': 1,
'number_of_polymer_residues': 186,
'number_of_polymers': 1,
'number_of_protein_chains': 1,
'organism_name': ['Homo sapiens',
'Man',
'Homo Sapiens (Human)',
'Human',
'Homo Sapiens',
'Homo sapiens',
'Homo',
'Homininae',
'Hominidae',
'Primates',
'Mammalia',
'Chordata',
'Metazoa',
'Eukaryota'],
'organism_scientific_name': ['Homo sapiens'],
'organism_synonyms': ['Man',
'Homo Sapiens (Human)',
'Human',
'Homo Sapiens',
'Homo sapiens',
'Homo',
'Homininae',
'Hominidae',
'Primates',
'Mammalia',
'Chordata',
'Metazoa',
'Eukaryota'],
'overall_quality': -73.0,
'pdb_accession': '1boz',
'pdb_format_compatible': 'Y',
'pdb_id': '1boz',
'percent_solvent': 52.93,
'pfam': ['PF00186 : DHFR_1'],
'pfam_accession': ['PF00186'],
'pfam_clan': ['CL0387 : DHFred'],
'pfam_clan_name': ['DHFred'],
'pfam_description': ['Dihydrofolate reductase'],
'pfam_name': ['DHFR_1'],
'pivot_resolution': 2.1,
'polymer_length': 186,
'prefered_assembly_id': '1',
'primary_wavelength': 1.5418,
'processing_site': 'RCSB',
'pubmed_author_list': ['Gangjee A, Vidwans AP, Vasudevan A, Queener SF, '
'Kisliuk RL, Cody V, Li R, Galitsky N, Luft JR, '
'Pangborn W'],
'pubmed_authors': ['Gangjee A',
'Vidwans AP',
'Vasudevan A',
'Queener SF',
'Kisliuk RL',
'Cody V',
'Li R',
'Galitsky N',
'Luft JR',
'Pangborn W'],
'pubmed_id': '9719595',
'q_abstracttext_unassigned': ['The synthesis and biological activities of 14 '
'6-substituted 2,4-diaminoquinazolines are '
'reported. These compounds were designed to '
'improve the cell penetration of a previously '
'reported series of '
'2,4-diamino-6-substituted-pyrido[2,3-d]pyrimidines '
'which had shown significant potency and '
'remarkable selectivity for Toxoplasma gondii '
'dihydrofolate reductase (DHFR), but had much '
'lower inhibitory effects on the growth of T. '
'gondii cells in culture. The target N9-H '
'analogues were obtained via regiospecific '
'reductive amination of the appropriate '
'benzaldehydes with 2,4,6-triaminoquinazoline, '
'which, in turn, was synthesized from '
'2,4-diamino-6-nitroquinazoline. The N9-CH3 '
'analogues were synthesized via a regiospecific '
'reductive methylation of the corresponding '
'N9-H precursors. The compounds were evaluated '
'as inhibitors of DHFR from human, Pneumocystis '
'carinii, T. gondii, rat liver, Lactobacillus '
'casei, and Escherichia coli, and selected '
'analogues were evaluated as inhibitors of the '
'growth of tumor cells in culture. These '
'analogues displayed potent T. gondii DHFR '
'inhibition as well as inhibition of the growth '
'of T. gondii cells in culture. Further, '
'selected analogues were potent inhibitors of '
'the growth of tumor cells in culture in the in '
'vitro screening program of the National Cancer '
'Institute with GI50s in the nanomolar and '
'subnanomolar range. Crystallographic data for '
'the ternary complex of hDHFR-NADPH and '
"2,4-diamino-6-[N-(2', "
"5'-dimethoxybenzyl)-N-methylamino]pyrido[2,3-d]pyrimidine, "
'1c, reveal the first structural details for a '
'reversed N9-C10 folate bridge geometry as well '
'as the first conformational details of a '
'hybrid piritrexim-trimetrexate analogue.'],
'q_all_assembly_composition': ['protein structure'],
'q_all_assembly_form': ['homo'],
'q_all_assembly_id': ['1'],
'q_all_assembly_mol_wt': [22.363],
'q_all_assembly_type': ['monomer'],
'q_all_authors': ['Cody V',
'Galitsky N',
'Gangjee A',
'Kisliuk RL',
'Li R',
'Luft JR',
'Pangborn W',
'Queener SF',
'Vasudevan A',
'Vidwans AP'],
'q_all_compound_names': ['PRD : '
'N6-(2,5-DIMETHOXY-BENZYL)-N6-METHYL-PYRIDO[2,3-D]PYRIMIDINE-2,4,6-TRIAMINE',
'NDP : NADPH '
'DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE',
'PRD : '
'N~6~-(2,5-dimethoxybenzyl)-N~6~-methylpyrido[2,3-d]pyrimidine-2,4,6-triamine',
'PRD : '
'N6-[(2,5-dimethoxyphenyl)methyl]-N6-methyl-pyrido[5,6-e]pyrimidine-2,4,6-triamine',
'NDP : '
'[[(2R,3S,4R,5R)-5-(3-aminocarbonyl-4H-pyridin-1-yl)-3,4-dihydroxy-oxolan-2-yl]methoxy-hydroxy-phosphoryl] '
'[(2R,3R,4R,5R)-5-(6-aminopurin-9-yl)-3-hydroxy-4-phosphonooxy-oxolan-2-yl]methyl '
'hydrogen phosphate'],
'q_all_enzyme_names': ['Oxidoreductases',
'Acting on the CH-NH group of donors',
'With NAD(+) or NADP(+) as acceptor',
'Dihydrofolate reductase',
'1.5.1.3 : Dihydrofolate reductase',
'5,6,7,8-tetrahydrofolate:NADP(+) oxidoreductase'],
'q_all_go_terms': ['cytoplasm',
'mitochondrion',
'cytosol',
'folic acid binding',
'oxidoreductase activity',
'NADPH binding',
'sequence-specific mRNA binding',
'RNA binding',
'mRNA binding',
'NADP binding',
'methotrexate binding',
'dihydrofolate reductase activity',
'translation repressor activity, mRNA regulatory element '
'binding',
'drug binding',
'one-carbon metabolic process',
'negative regulation of translation',
'folic acid metabolic process',
'response to methotrexate',
'regulation of removal of superoxide radicals',
'tetrahydrofolate metabolic process',
'tetrahydrobiopterin biosynthetic process',
'tetrahydrofolate biosynthetic process',
'positive regulation of nitric-oxide synthase activity',
'regulation of transcription involved in G1/S transition '
'of mitotic cell cycle',
'oxidation-reduction process',
'axon regeneration',
'dihydrofolate metabolic process'],
'q_all_molecule_names': ['Dihydrofolate reductase', 'Dihydrofolate reductase'],
'q_all_num_interacting_entity_id': [0],
'q_all_sequence_family': ['IPR001796 : Dihydrofolate reductase domain',
'IPR024072 : Dihydrofolate reductase-like domain '
'superfamily',
'PF00186 : DHFR_1',
'CL0387 : DHFred'],
'q_all_structure_family': ['3-Layer(aba) Sandwich',
'Alpha Beta',
'3.40.430.10',
'Dihydrofolate Reductase, subunit A',
'Dihydrofolate Reductase, subunit A',
'Alpha and beta proteins (a/b)',
'Dihydrofolate reductases',
'Dihydrofolate reductase-like',
'Dihydrofolate reductase-like'],
'q_assembly_composition': ['protein structure'],
'q_assembly_form': ['homo'],
'q_assembly_id': ['1'],
'q_assembly_mol_wt': 22.363,
'q_assembly_num_component': [1],
'q_assembly_type': ['monomer'],
'q_beam_source_name': ['Rotating anode'],
'q_biological_cell_component': ['cytoplasm', 'mitochondrion', 'cytosol'],
'q_biological_function': ['folic acid binding',
'oxidoreductase activity',
'NADPH binding',
'sequence-specific mRNA binding',
'RNA binding',
'mRNA binding',
'NADP binding',
'methotrexate binding',
'dihydrofolate reductase activity',
'translation repressor activity, mRNA regulatory '
'element binding',
'drug binding'],
'q_biological_process': ['one-carbon metabolic process',
'negative regulation of translation',
'folic acid metabolic process',
'response to methotrexate',
'regulation of removal of superoxide radicals',
'tetrahydrofolate metabolic process',
'tetrahydrobiopterin biosynthetic process',
'tetrahydrofolate biosynthetic process',
'positive regulation of nitric-oxide synthase '
'activity',
'regulation of transcription involved in G1/S '
'transition of mitotic cell cycle',
'oxidation-reduction process',
'axon regeneration',
'dihydrofolate metabolic process'],
'q_bound_compound_id': ['PRD', 'NDP'],
'q_bound_compound_name': ['PRD : '
'N6-(2,5-DIMETHOXY-BENZYL)-N6-METHYL-PYRIDO[2,3-D]PYRIMIDINE-2,4,6-TRIAMINE',
'NDP : NADPH '
'DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE '
'PHOSPHATE'],
'q_bound_compound_systematic_name': ['PRD : '
'N~6~-(2,5-dimethoxybenzyl)-N~6~-methylpyrido[2,3-d]pyrimidine-2,4,6-triamine',
'PRD : '
'N6-[(2,5-dimethoxyphenyl)methyl]-N6-methyl-pyrido[5,6-e]pyrimidine-2,4,6-triamine',
'NDP : '
'[[(2R,3S,4R,5R)-5-(3-aminocarbonyl-4H-pyridin-1-yl)-3,4-dihydroxy-oxolan-2-yl]methoxy-hydroxy-phosphoryl] '
'[(2R,3R,4R,5R)-5-(6-aminopurin-9-yl)-3-hydroxy-4-phosphonooxy-oxolan-2-yl]methyl '
'hydrogen phosphate'],
'q_bound_compound_weight': [340.38, 745.421],
'q_cath_architecture': ['3-Layer(aba) Sandwich'],
'q_cath_class': ['Alpha Beta'],
'q_cath_code': ['3.40.430.10'],
'q_cath_homologous_superfamily': ['Dihydrofolate Reductase, subunit A'],
'q_cath_topology': ['Dihydrofolate Reductase, subunit A'],
'q_cell_a': 86.259,
'q_cell_alpha': 90.0,
'q_cell_b': 86.259,
'q_cell_beta': 90.0,
'q_cell_c': 77.637,
'q_cell_gamma': 120.0,
'q_citation_authors': ['Gangjee A',
'Vidwans AP',
'Vasudevan A',
'Queener SF',
'Kisliuk RL',
'Cody V',
'Li R',
'Galitsky N',
'Luft JR',
'Pangborn W'],
'q_citation_doi': '10.1021/jm980081y',
'q_citation_title': 'Structure-based design and synthesis of lipophilic '
'2,4-diamino-6-substituted quinazolines and their '
'evaluation as inhibitors of dihydrofolate reductases and '
'potential antitumor agents.',
'q_citation_year': 1998,
'q_cofactor_class': ['Nicotinamide-adenine dinucleotide'],
'q_cofactor_id': ['NDP'],
'q_compound_id': ['PRD', 'NDP'],
'q_compound_name': ['PRD : '
'N6-(2,5-DIMETHOXY-BENZYL)-N6-METHYL-PYRIDO[2,3-D]PYRIMIDINE-2,4,6-TRIAMINE',
'NDP : NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE '
'PHOSPHATE'],
'q_compound_systematic_name': ['PRD : '
'N~6~-(2,5-dimethoxybenzyl)-N~6~-methylpyrido[2,3-d]pyrimidine-2,4,6-triamine',
'PRD : '
'N6-[(2,5-dimethoxyphenyl)methyl]-N6-methyl-pyrido[5,6-e]pyrimidine-2,4,6-triamine',
'NDP : '
'[[(2R,3S,4R,5R)-5-(3-aminocarbonyl-4H-pyridin-1-yl)-3,4-dihydroxy-oxolan-2-yl]methoxy-hydroxy-phosphoryl] '
'[(2R,3R,4R,5R)-5-(6-aminopurin-9-yl)-3-hydroxy-4-phosphonooxy-oxolan-2-yl]methyl '
'hydrogen phosphate'],
'q_compound_weight': [340.38, 745.421],
'q_crystallisation_cond': ['pH 6.5'],
'q_crystallisation_ph': [6.5],
'q_data_quality': -1.0,
'q_data_scaling_software': ['SCALEPACK'],
'q_deposition_date': '1998-08-06T01:00:00Z',
'q_deposition_site': 'BNL',
'q_deposition_year': 1998,
'q_detector': ['Image plate'],
'q_detector_type': ['RIGAKU RAXIS'],
'q_diffraction_protocol': ['Single wavelength'],
'q_diffraction_source_type': ['RIGAKU RU200'],
'q_diffraction_wavelengths': [1.5418],
'q_ec_hierarchy_name': ['Oxidoreductases',
'Acting on the CH-NH group of donors',
'With NAD(+) or NADP(+) as acceptor',
'Dihydrofolate reductase'],
'q_ec_number': ['1.5.1.3'],
'q_entity_id': 1,
'q_entity_weight': 21259.402,
'q_entry_author_list': ['Gangjee A, Vidwans AP, Vasudevan A, Queener SF, '
'Kisliuk RL, Cody V, Li R, Galitsky N, Luft JR, '
'Pangborn W'],
'q_entry_authors': ['Gangjee A',
'Vidwans AP',
'Vasudevan A',
'Queener SF',
'Kisliuk RL',
'Cody V',
'Li R',
'Galitsky N',
'Luft JR',
'Pangborn W'],
'q_entry_lig_entity': ['1boz_PRD_3', '1boz_NDP_2'],
'q_enzyme_name': ['Dihydrofolate reductase'],
'q_enzyme_num_name': ['1.5.1.3 : Dihydrofolate reductase'],
'q_enzyme_systematic_name': ['5,6,7,8-tetrahydrofolate:NADP(+) '
'oxidoreductase'],
'q_experimental_method': ['X-ray diffraction'],
'q_gene_name': ['DHFR'],
'q_genus': ['Homo'],
'q_go_id': ['GO:0006730',
'GO:0017148',
'GO:0046655',
'GO:0031427',
'GO:2000121',
'GO:0046653',
'GO:0006729',
'GO:0046654',
'GO:0051000',
'GO:0000083',
'GO:0055114',
'GO:0031103',
'GO:0046452',
'GO:0005542',
'GO:0016491',
'GO:0070402',
'GO:1990825',
'GO:0003723',
'GO:0003729',
'GO:0050661',
'GO:0051870',
'GO:0004146',
'GO:0000900',
'GO:0008144',
'GO:0005737',
'GO:0005739',
'GO:0005829'],
'q_go_mapping': ['GO:0006730 : one-carbon metabolic process',
'GO:0017148 : negative regulation of translation',
'GO:0046655 : folic acid metabolic process',
'GO:0031427 : response to methotrexate',
'GO:2000121 : regulation of removal of superoxide radicals',
'GO:0046653 : tetrahydrofolate metabolic process',
'GO:0006729 : tetrahydrobiopterin biosynthetic process',
'GO:0046654 : tetrahydrofolate biosynthetic process',
'GO:0051000 : positive regulation of nitric-oxide synthase '
'activity',
'GO:0000083 : regulation of transcription involved in G1/S '
'transition of mitotic cell cycle',
'GO:0055114 : oxidation-reduction process',
'GO:0031103 : axon regeneration',
'GO:0046452 : dihydrofolate metabolic process',
'GO:0005542 : folic acid binding',
'GO:0016491 : oxidoreductase activity',
'GO:0070402 : NADPH binding',
'GO:1990825 : sequence-specific mRNA binding',
'GO:0003723 : RNA binding',
'GO:0003729 : mRNA binding',
'GO:0050661 : NADP binding',
'GO:0051870 : methotrexate binding',
'GO:0004146 : dihydrofolate reductase activity',
'GO:0000900 : translation repressor activity, mRNA '
'regulatory element binding',
'GO:0008144 : drug binding',
'GO:0005737 : cytoplasm',
'GO:0005739 : mitochondrion',
'GO:0005829 : cytosol'],
'q_has_bound_molecule': 'Y',
'q_has_modified_residues': 'N',
'q_homologus_pdb_entity_id': ['4qhv_1',
'6dav_1',
'1dlr_1',
'4kak_1',
'4keb_1',
'5hqy_1',
'5hqz_1',
'1u72_1',
'2w3b_1',
'5hsr_1',
'5ht4_1',
'3nu0_1',
'3nxo_1',
'3nxt_1',
'3nxv_1',
'2c2s_1',
'3nxr_1',
'1hfr_1',
'1s3v_1',
'1s3w_1',
'1u71_1',
'1yho_1',
'2w3a_1',
'3nxy_1',
'3nzd_1',
'3s7a_1',
'5hve_1',
'1dls_1',
'1drf_1',
'1mvs_1',
'2c2t_1',
'4m6j_1',
'1kms_1',
'1pd9_1',
'3ghc_1',
'3ghw_1',
'3ntz_1',
'3nxx_1',
'1pdb_1',
'3f8y_1',
'3gi2_1',
'6a7e_1',
'1pd8_1',
'4ddr_1',
'4m6k_1',
'3f8z_1',
'3f91_1',
'3fs6_1',
'4m6l_1',
'4qjc_1',
'5hsu_1',
'1boz_1',
'3n0h_1',
'4kfj_1',
'1kmv_1',
'1mvt_1',
'3oaf_1',
'4kd7_1',
'5hpb_1',
'6a7c_1',
'1ohj_1',
'3gyf_1',
'4g95_1',
'5hui_1',
'1dhf_1',
'1s3u_1',
'2dhf_1',
'3ghv_1',
'1hfp_1',
'1hfq_1',
'1ohk_1',
'2w3m_1',
'3eig_1',
'3l3r_1',
'3s3v_1',
'4kbn_1',
'5ht5_1',
'5hvb_1',
'6de4_1'],
'q_interacting_ligands': ['PRD : '
'N6-(2,5-DIMETHOXY-BENZYL)-N6-METHYL-PYRIDO[2,3-D]PYRIMIDINE-2,4,6-TRIAMINE',
'NDP : NADPH '
'DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE '
'PHOSPHATE'],
'q_interpro': ['IPR001796 : Dihydrofolate reductase domain',
'IPR024072 : Dihydrofolate reductase-like domain superfamily'],
'q_interpro_accession': ['IPR001796', 'IPR024072'],
'q_interpro_name': ['Dihydrofolate reductase domain',
'Dihydrofolate reductase-like domain superfamily'],
'q_inv_overall_quality': 173.0,
'q_journal': 'J. Med. Chem.',
'q_journal_page': '3426-34',
'q_journal_volume': '41',
'q_matthews_coefficient': 2.61,
'q_max_observed_residues': 186,
'q_mesh_terms': 'Animals,Antineoplastic Agents,Cell Division,Crystallography, '
'X-Ray,Drug Design,Drug Screening Assays, '
'Antitumor,Escherichia coli,Folic Acid '
'Antagonists,Humans,Liver,Models, Molecular,Molecular '
'Structure,NADP,Pneumocystis,Pyridines,Pyrimidines,Quinazolines,Rats,Structure-Activity '
'Relationship,Tetrahydrofolate Dehydrogenase,Toxoplasma,Tumor '
'Cells, Cultured',
'q_model_quality': 16.12,
'q_modified_residue_flag': 'N',
'q_molecule_name': ['Dihydrofolate reductase'],
'q_molecule_sequence': 'VGSLNCIVAVSQNMGIGKNGDLPWPPLRNEGRYFQRMTTTSSVEGKQNLVIMGKKTWFSIPEKNRPLKGRINLVLSRELKEPPQGAHFLSRSLDDALKLTEQPELANKVDMVWIVGGSSVYKEAMNHPGHLKLFVTRIMQDFESDTFFPEIDLEKYKLLPEYPGVLSDVQEEKGIKYKFEVYEKND',
'q_molecule_synonym': ['Dihydrofolate reductase'],
'q_molecule_type': 'Protein',
'q_mutation': 'y',
'q_mutation_info': ['F31G'],
'q_mutation_type': ['Conflict'],
'q_nigli_cell_a': 56.124,
'q_nigli_cell_alpha': 100.433,
'q_nigli_cell_b': 56.124,
'q_nigli_cell_beta': 100.433,
'q_nigli_cell_c': 56.124,
'q_nigli_cell_gamma': 100.433,
'q_nigli_cell_symmetry': 'R32',
'q_num_interacting_entity_id': [0],
'q_number_of_bound_entities': 2,
'q_number_of_bound_molecules': 2,
'q_number_of_copies': 1,
'q_number_of_models': 1,
'q_number_of_polymer_entities': 1,
'q_number_of_polymer_residues': 186,
'q_number_of_polymers': 1,
'q_number_of_protein_chains': 1,
'q_organism_name': ['Homo sapiens',
'Man',
'Homo Sapiens (Human)',
'Human',
'Homo Sapiens',
'Homo sapiens',
'Homo',
'Homininae',
'Hominidae',
'Primates',
'Mammalia',
'Chordata',
'Metazoa',
'Eukaryota'],
'q_organism_scientific_name': ['Homo sapiens'],
'q_organism_synonyms': ['Man',
'Homo Sapiens (Human)',
'Human',
'Homo Sapiens',
'Homo sapiens',
'Homo',
'Homininae',
'Hominidae',
'Primates',
'Mammalia',
'Chordata',
'Metazoa',
'Eukaryota'],
'q_overall_quality': -73.0,
'q_pdb_accession': '1boz',
'q_pdb_format_compatible': 'Y',
'q_pdb_id': '1boz',
'q_percent_solvent': 52.93,
'q_pfam': ['PF00186 : DHFR_1'],
'q_pfam_accession': ['PF00186'],
'q_pfam_clan': ['CL0387 : DHFred'],
'q_pfam_clan_name': ['DHFred'],
'q_pfam_description': ['Dihydrofolate reductase'],
'q_pfam_name': ['DHFR_1'],
'q_pivot_resolution': 2.1,
'q_polymer_length': 186,
'q_prefered_assembly_id': '1',
'q_primary_wavelength': 1.5418,
'q_processing_site': 'RCSB',
'q_pubmed_author_list': ['Gangjee A, Vidwans AP, Vasudevan A, Queener SF, '
'Kisliuk RL, Cody V, Li R, Galitsky N, Luft JR, '
'Pangborn W'],
'q_pubmed_authors': ['Gangjee A',
'Vidwans AP',
'Vasudevan A',
'Queener SF',
'Kisliuk RL',
'Cody V',
'Li R',
'Galitsky N',
'Luft JR',
'Pangborn W'],
'q_pubmed_id': '9719595',
'q_r_factor': 0.202,
'q_r_work': [0.202],
'q_rank': ['species',
'genus',
'subfamily',
'family',
'order',
'class',
'phylum',
'kingdom',
'superkingdom'],
'q_refinement_software': ['PROLSQ'],
'q_release_date': '1998-08-12T01:00:00Z',
'q_release_year': 1998,
'q_resolution': 2.1,
'q_revision_date': '2017-10-04T01:00:00Z',
'q_revision_year': 2017,
'q_sample_preparation_method': ['Natural'],
'q_scop_class': ['Alpha and beta proteins (a/b)'],
'q_scop_family': ['Dihydrofolate reductases'],
'q_scop_fold': ['Dihydrofolate reductase-like'],
'q_scop_superfamily': ['Dihydrofolate reductase-like'],
'q_seq_100_cluster_number': '57152',
'q_seq_100_cluster_rank': 2,
'q_seq_30_cluster_number': '20247',
'q_seq_30_cluster_rank': 48,
'q_seq_40_cluster_number': '18848',
'q_seq_40_cluster_rank': 48,
'q_seq_50_cluster_number': '24957',
'q_seq_50_cluster_rank': 48,
'q_seq_70_cluster_number': '17116',
'q_seq_70_cluster_rank': 48,
'q_seq_90_cluster_number': '1443',
'q_seq_90_cluster_rank': 42,
'q_seq_95_cluster_number': '55620',
'q_seq_95_cluster_rank': 36,
'q_spacegroup': 'H 3',
'q_status': 'REL',
'q_struct_asym_id': ['A'],
'q_structure_determination_method': ['MOLECULAR REPLACEMENT'],
'q_superkingdom': ['Eukaryota'],
'q_tax_id': [9606],
'q_tax_query': [9606],
'q_title': 'STRUCTURE-BASED DESIGN AND SYNTHESIS OF LIPOPHILIC '
'2,4-DIAMINO-6-SUBSTITUTED QUINAZOLINES AND THEIR EVALUATION AS '
'INHIBITORS OF DIHYDROFOLATE REDUCTASE AND POTENTIAL ANTITUMOR '
'AGENTS',
'q_uniprot': ['P00374 : DYR_HUMAN'],
'q_uniprot_accession': ['P00374', 'P00374-2'],
'q_uniprot_accession_best': ['P00374-2'],
'q_uniprot_best': ['P00374-2 : DYR_HUMAN'],
'q_uniprot_coverage': [0.99],
'q_uniprot_features': ['Protein has possible alternate isoforms',
'DHFR',
'Nucleotide binding - NADP',
'Protein has possible natural variant '],
'q_uniprot_id': ['DYR_HUMAN', 'DYR_HUMAN'],
'q_uniprot_id_best': ['DYR_HUMAN'],
'q_uniprot_non_canonical': ['P00374-2 : DYR_HUMAN'],
'q_unp_count': 1,
'q_unp_nf90_accession': ['B0YJ76',
'A0A2K6C3Y8',
'P00374',
'A0A024RAQ3',
'S5WD14',
'S5VM81'],
'q_unp_nf90_id': ['B0YJ76_HUMAN',
'A0A2K6C3Y8_MACNE',
'DYR_HUMAN',
'A0A024RAQ3_HUMAN',
'S5WD14_SHISS',
'S5VM81_ECO57'],
'q_unp_nf90_organism': ['Homo sapiens (Human)',
'Macaca nemestrina (Pig-tailed macaque)',
'Homo sapiens (Human)',
'Homo sapiens (Human)',
'Shigella sonnei (strain Ss046)',
'Escherichia coli O157:H7'],
'q_unp_nf90_protein_name': ['Dihydrofolate reductase',
'DHFR domain-containing protein',
'Dihydrofolate reductase',
'Dihydrofolate reductase, isoform CRA_a',
'Trimethoprim resistant protein',
'Trimethoprim resistant protein'],
'q_unp_nf90_tax_id': ['9606', '9545', '9606', '9606', '300269', '83334'],
'r_factor': 0.202,
'r_work': [0.202],
'rank': ['species',
'genus',
'subfamily',
'family',
'order',
'class',
'phylum',
'kingdom',
'superkingdom'],
'refinement_software': ['PROLSQ'],
'release_date': '1998-08-12T01:00:00Z',
'release_year': 1998,
'resolution': 2.1,
'revision_date': '2017-10-04T01:00:00Z',
'revision_year': 2017,
'sample_preparation_method': ['Natural'],
'scop_class': ['Alpha and beta proteins (a/b)'],
'scop_family': ['Dihydrofolate reductases'],
'scop_fold': ['Dihydrofolate reductase-like'],
'scop_superfamily': ['Dihydrofolate reductase-like'],
'seq_100_cluster_number': '57152',
'seq_100_cluster_rank': 2,
'seq_30_cluster_number': '20247',
'seq_30_cluster_rank': 48,
'seq_40_cluster_number': '18848',
'seq_40_cluster_rank': 48,
'seq_50_cluster_number': '24957',
'seq_50_cluster_rank': 48,
'seq_70_cluster_number': '17116',
'seq_70_cluster_rank': 48,
'seq_90_cluster_number': '1443',
'seq_90_cluster_rank': 42,
'seq_95_cluster_number': '55620',
'seq_95_cluster_rank': 36,
'spacegroup': 'H 3',
'status': 'REL',
'struct_asym_id': ['A'],
'structure_determination_method': ['MOLECULAR REPLACEMENT'],
'superkingdom': ['Eukaryota'],
't_abstracttext_unassigned': ['The synthesis and biological activities of 14 '
'6-substituted 2,4-diaminoquinazolines are '
'reported. These compounds were designed to '
'improve the cell penetration of a previously '
'reported series of '
'2,4-diamino-6-substituted-pyrido[2,3-d]pyrimidines '
'which had shown significant potency and '
'remarkable selectivity for Toxoplasma gondii '
'dihydrofolate reductase (DHFR), but had much '
'lower inhibitory effects on the growth of T. '
'gondii cells in culture. The target N9-H '
'analogues were obtained via regiospecific '
'reductive amination of the appropriate '
'benzaldehydes with 2,4,6-triaminoquinazoline, '
'which, in turn, was synthesized from '
'2,4-diamino-6-nitroquinazoline. The N9-CH3 '
'analogues were synthesized via a regiospecific '
'reductive methylation of the corresponding '
'N9-H precursors. The compounds were evaluated '
'as inhibitors of DHFR from human, Pneumocystis '
'carinii, T. gondii, rat liver, Lactobacillus '
'casei, and Escherichia coli, and selected '
'analogues were evaluated as inhibitors of the '
'growth of tumor cells in culture. These '
'analogues displayed potent T. gondii DHFR '
'inhibition as well as inhibition of the growth '
'of T. gondii cells in culture. Further, '
'selected analogues were potent inhibitors of '
'the growth of tumor cells in culture in the in '
'vitro screening program of the National Cancer '
'Institute with GI50s in the nanomolar and '
'subnanomolar range. Crystallographic data for '
'the ternary complex of hDHFR-NADPH and '
"2,4-diamino-6-[N-(2', "
"5'-dimethoxybenzyl)-N-methylamino]pyrido[2,3-d]pyrimidine, "
'1c, reveal the first structural details for a '
'reversed N9-C10 folate bridge geometry as well '
'as the first conformational details of a '
'hybrid piritrexim-trimetrexate analogue.'],
't_all_compound_names': ['Nicotinamide-adenine dinucleotide',
'NDP',
'PRD : '
'N6-(2,5-DIMETHOXY-BENZYL)-N6-METHYL-PYRIDO[2,3-D]PYRIMIDINE-2,4,6-TRIAMINE',
'NDP : NADPH '
'DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE',
'PRD : '
'N~6~-(2,5-dimethoxybenzyl)-N~6~-methylpyrido[2,3-d]pyrimidine-2,4,6-triamine',
'PRD : '
'N6-[(2,5-dimethoxyphenyl)methyl]-N6-methyl-pyrido[5,6-e]pyrimidine-2,4,6-triamine',
'NDP : '
'[[(2R,3S,4R,5R)-5-(3-aminocarbonyl-4H-pyridin-1-yl)-3,4-dihydroxy-oxolan-2-yl]methoxy-hydroxy-phosphoryl] '
'[(2R,3R,4R,5R)-5-(6-aminopurin-9-yl)-3-hydroxy-4-phosphonooxy-oxolan-2-yl]methyl '
'hydrogen phosphate'],
't_all_enzyme_names': ['Oxidoreductases',
'Acting on the CH-NH group of donors',
'With NAD(+) or NADP(+) as acceptor',
'Dihydrofolate reductase',
'1.5.1.3 : Dihydrofolate reductase',
'5,6,7,8-tetrahydrofolate:NADP(+) oxidoreductase'],
't_all_go_terms': ['cytoplasm',
'mitochondrion',
'cytosol',
'folic acid binding',
'oxidoreductase activity',
'NADPH binding',
'sequence-specific mRNA binding',
'RNA binding',
'mRNA binding',
'NADP binding',
'methotrexate binding',
'dihydrofolate reductase activity',
'translation repressor activity, mRNA regulatory element '
'binding',
'drug binding',
'one-carbon metabolic process',
'negative regulation of translation',
'folic acid metabolic process',
'response to methotrexate',
'regulation of removal of superoxide radicals',
'tetrahydrofolate metabolic process',
'tetrahydrobiopterin biosynthetic process',
'tetrahydrofolate biosynthetic process',
'positive regulation of nitric-oxide synthase activity',
'regulation of transcription involved in G1/S transition '
'of mitotic cell cycle',
'oxidation-reduction process',
'axon regeneration',
'dihydrofolate metabolic process'],
't_all_sequence_family': ['IPR001796 : Dihydrofolate reductase domain',
'IPR024072 : Dihydrofolate reductase-like domain '
'superfamily',
'PF00186 : DHFR_1',
'CL0387 : DHFred'],
't_all_structure_family': ['3-Layer(aba) Sandwich',
'Alpha Beta',
'3.40.430.10',
'Dihydrofolate Reductase, subunit A',
'Dihydrofolate Reductase, subunit A',
'Alpha and beta proteins (a/b)',
'Dihydrofolate reductases',
'Dihydrofolate reductase-like',
'Dihydrofolate reductase-like'],
't_citation_authors': ['Gangjee A',
'Vidwans AP',
'Vasudevan A',
'Queener SF',
'Kisliuk RL',
'Cody V',
'Li R',
'Galitsky N',
'Luft JR',
'Pangborn W'],
't_citation_title': ['Structure-based design and synthesis of lipophilic '
'2,4-diamino-6-substituted quinazolines and their '
'evaluation as inhibitors of dihydrofolate reductases '
'and potential antitumor agents.'],
't_entry_authors': ['Gangjee A',
'Vidwans AP',
'Vasudevan A',
'Queener SF',
'Kisliuk RL',
'Cody V',
'Li R',
'Galitsky N',
'Luft JR',
'Pangborn W'],
't_entry_info': ['SCALEPACK',
'Image plate',
'RIGAKU RAXIS',
'X-ray diffraction',
'PROLSQ',
'MOLECULAR REPLACEMENT'],
't_entry_title': ['STRUCTURE-BASED DESIGN AND SYNTHESIS OF LIPOPHILIC '
'2,4-DIAMINO-6-SUBSTITUTED QUINAZOLINES AND THEIR '
'EVALUATION AS INHIBITORS OF DIHYDROFOLATE REDUCTASE AND '
'POTENTIAL ANTITUMOR AGENTS'],
't_journal': ['J. Med. Chem.'],
't_mesh_terms': ['Animals,Antineoplastic Agents,Cell '
'Division,Crystallography, X-Ray,Drug Design,Drug Screening '
'Assays, Antitumor,Escherichia coli,Folic Acid '
'Antagonists,Humans,Liver,Models, Molecular,Molecular '
'Structure,NADP,Pneumocystis,Pyridines,Pyrimidines,Quinazolines,Rats,Structure-Activity '
'Relationship,Tetrahydrofolate '
'Dehydrogenase,Toxoplasma,Tumor Cells, Cultured'],
't_molecule_info': ['protein structure',
'homo',
'monomer',
'Dihydrofolate reductase',
'Dihydrofolate reductase',
'protein structure',
'homo',
'monomer',
'DHFR',
'P00374',
'P00374-2',
'Protein has possible alternate isoforms',
'DHFR',
'Nucleotide binding - NADP',
'Protein has possible natural variant ',
'DYR_HUMAN',
'DYR_HUMAN'],
't_molecule_sequence': 'VGSLNCIVAVSQNMGIGKNGDLPWPPLRNEGRYFQRMTTTSSVEGKQNLVIMGKKTWFSIPEKNRPLKGRINLVLSRELKEPPQGAHFLSRSLDDALKLTEQPELANKVDMVWIVGGSSVYKEAMNHPGHLKLFVTRIMQDFESDTFFPEIDLEKYKLLPEYPGVLSDVQEEKGIKYKFEVYEKND',
't_organism_name': ['Homo sapiens',
'Man',
'Homo Sapiens (Human)',
'Human',
'Homo Sapiens',
'Homo sapiens',
'Homo',
'Homininae',
'Hominidae',
'Primates',
'Mammalia',
'Chordata',
'Metazoa',
'Eukaryota'],
'tax_id': [9606],
'tax_query': [9606],
'title': 'STRUCTURE-BASED DESIGN AND SYNTHESIS OF LIPOPHILIC '
'2,4-DIAMINO-6-SUBSTITUTED QUINAZOLINES AND THEIR EVALUATION AS '
'INHIBITORS OF DIHYDROFOLATE REDUCTASE AND POTENTIAL ANTITUMOR '
'AGENTS',
'uniprot': ['P00374 : DYR_HUMAN'],
'uniprot_accession': ['P00374', 'P00374-2'],
'uniprot_accession_best': ['P00374-2'],
'uniprot_best': ['P00374-2 : DYR_HUMAN'],
'uniprot_coverage': [0.99],
'uniprot_features': ['Protein has possible alternate isoforms',
'DHFR',
'Nucleotide binding - NADP',
'Protein has possible natural variant '],
'uniprot_id': ['DYR_HUMAN', 'DYR_HUMAN'],
'uniprot_id_best': ['DYR_HUMAN'],
'uniprot_non_canonical': ['P00374-2 : DYR_HUMAN'],
'unp_count': 1,
'unp_nf90_accession': ['B0YJ76',
'A0A2K6C3Y8',
'P00374',
'A0A024RAQ3',
'S5WD14',
'S5VM81'],
'unp_nf90_id': ['B0YJ76_HUMAN',
'A0A2K6C3Y8_MACNE',
'DYR_HUMAN',
'A0A024RAQ3_HUMAN',
'S5WD14_SHISS',
'S5VM81_ECO57'],
'unp_nf90_organism': ['Homo sapiens (Human)',
'Macaca nemestrina (Pig-tailed macaque)',
'Homo sapiens (Human)',
'Homo sapiens (Human)',
'Shigella sonnei (strain Ss046)',
'Escherichia coli O157:H7'],
'unp_nf90_protein_name': ['Dihydrofolate reductase',
'DHFR domain-containing protein',
'Dihydrofolate reductase',
'Dihydrofolate reductase, isoform CRA_a',
'Trimethoprim resistant protein',
'Trimethoprim resistant protein'],
'unp_nf90_tax_id': ['9606', '9545', '9606', '9606', '300269', '83334']}
As you can see we get lots of data back about the individual molecule we have searched for and the PDB entries in which it is contained.
We can get the PDB ID and experimental method for this first row as follows.
[9]:
print(results[0].get('pdb_id'))
print(results[0].get('experimental_method'))
1boz
['X-ray diffraction']
We can restrict the results to only the information we want using a filter so its easier to see the information we want.
[10]:
print('3rd search')
search_terms = {"molecule_name":"Dihydrofolate reductase",
"organism_name":"Human"
}
filter_terms = ['pdb_id', 'experimental_method']
results = run_search(search_terms, filter_terms)
pprint(results)
3rd search
https://www.ebi.ac.uk/pdbe/search/pdb/select?q=molecule_name:"Dihydrofolate reductase" AND organism_name:Human&fl=pdb_id,experimental_method&wt=json&rows=100
Number of results for Dihydrofolate reductase,Human: 79
[{'experimental_method': ['X-ray diffraction'], 'pdb_id': '1boz'},
{'experimental_method': ['X-ray diffraction'], 'pdb_id': '1pd8'},
{'experimental_method': ['X-ray diffraction'], 'pdb_id': '6a7e'},
{'experimental_method': ['X-ray diffraction'], 'pdb_id': '4kbn'},
{'experimental_method': ['X-ray diffraction'], 'pdb_id': '4kd7'},
{'experimental_method': ['X-ray diffraction'], 'pdb_id': '4qhv'},
{'experimental_method': ['X-ray diffraction'], 'pdb_id': '1mvt'},
{'experimental_method': ['X-ray diffraction'], 'pdb_id': '3ghv'},
{'experimental_method': ['X-ray diffraction'], 'pdb_id': '3fs6'},
{'experimental_method': ['X-ray diffraction'], 'pdb_id': '3ntz'},
{'experimental_method': ['X-ray diffraction'], 'pdb_id': '3gyf'},
{'experimental_method': ['X-ray diffraction'], 'pdb_id': '5ht4'},
{'experimental_method': ['X-ray diffraction'], 'pdb_id': '2w3m'},
{'experimental_method': ['X-ray diffraction'], 'pdb_id': '6de4'},
{'experimental_method': ['X-ray diffraction'], 'pdb_id': '4m6j'},
{'experimental_method': ['X-ray diffraction'], 'pdb_id': '5hui'},
{'experimental_method': ['X-ray diffraction'], 'pdb_id': '5hqy'},
{'experimental_method': ['X-ray diffraction'], 'pdb_id': '1hfp'},
{'experimental_method': ['X-ray diffraction'], 'pdb_id': '4kfj'},
{'experimental_method': ['X-ray diffraction'], 'pdb_id': '6dav'},
{'experimental_method': ['X-ray diffraction'], 'pdb_id': '4keb'},
{'experimental_method': ['X-ray diffraction'], 'pdb_id': '5hsu'},
{'experimental_method': ['X-ray diffraction'], 'pdb_id': '4kak'},
{'experimental_method': ['X-ray diffraction'], 'pdb_id': '4ddr'},
{'experimental_method': ['X-ray diffraction'], 'pdb_id': '1hfr'},
{'experimental_method': ['X-ray diffraction'], 'pdb_id': '3nxt'},
{'experimental_method': ['X-ray diffraction'], 'pdb_id': '1pd9'},
{'experimental_method': ['X-ray diffraction'], 'pdb_id': '1s3v'},
{'experimental_method': ['X-ray diffraction'], 'pdb_id': '3s7a'},
{'experimental_method': ['X-ray diffraction'], 'pdb_id': '5hpb'},
{'experimental_method': ['X-ray diffraction'], 'pdb_id': '3s3v'},
{'experimental_method': ['X-ray diffraction'], 'pdb_id': '1dlr'},
{'experimental_method': ['X-ray diffraction'], 'pdb_id': '1dls'},
{'experimental_method': ['X-ray diffraction'], 'pdb_id': '3nxo'},
{'experimental_method': ['X-ray diffraction'], 'pdb_id': '3n0h'},
{'experimental_method': ['X-ray diffraction'], 'pdb_id': '3eig'},
{'experimental_method': ['X-ray diffraction'], 'pdb_id': '3nxx'},
{'experimental_method': ['X-ray diffraction'], 'pdb_id': '1ohj'},
{'experimental_method': ['X-ray diffraction'], 'pdb_id': '2dhf'},
{'experimental_method': ['X-ray diffraction'], 'pdb_id': '5hvb'},
{'experimental_method': ['X-ray diffraction'], 'pdb_id': '3nxr'},
{'experimental_method': ['X-ray diffraction'], 'pdb_id': '1pdb'},
{'experimental_method': ['X-ray diffraction'], 'pdb_id': '1drf'},
{'experimental_method': ['X-ray diffraction'], 'pdb_id': '1mvs'},
{'experimental_method': ['X-ray diffraction'], 'pdb_id': '1s3w'},
{'experimental_method': ['X-ray diffraction'], 'pdb_id': '2c2t'},
{'experimental_method': ['X-ray diffraction'], 'pdb_id': '3oaf'},
{'experimental_method': ['X-ray diffraction'], 'pdb_id': '5ht5'},
{'experimental_method': ['X-ray diffraction'], 'pdb_id': '3f91'},
{'experimental_method': ['X-ray diffraction'], 'pdb_id': '3ghw'},
{'experimental_method': ['X-ray diffraction'], 'pdb_id': '4qjc'},
{'experimental_method': ['X-ray diffraction'], 'pdb_id': '3nu0'},
{'experimental_method': ['X-ray diffraction'], 'pdb_id': '1kms'},
{'experimental_method': ['X-ray diffraction'], 'pdb_id': '1u71'},
{'experimental_method': ['X-ray diffraction'], 'pdb_id': '1dhf'},
{'experimental_method': ['X-ray diffraction'], 'pdb_id': '3ghc'},
{'experimental_method': ['X-ray diffraction'], 'pdb_id': '3nzd'},
{'experimental_method': ['X-ray diffraction'], 'pdb_id': '2w3b'},
{'experimental_method': ['X-ray diffraction'], 'pdb_id': '2w3a'},
{'experimental_method': ['X-ray diffraction'], 'pdb_id': '3gi2'},
{'experimental_method': ['X-ray diffraction'], 'pdb_id': '1ohk'},
{'experimental_method': ['X-ray diffraction'], 'pdb_id': '4m6k'},
{'experimental_method': ['X-ray diffraction'], 'pdb_id': '1s3u'},
{'experimental_method': ['X-ray diffraction'], 'pdb_id': '5hve'},
{'experimental_method': ['X-ray diffraction'], 'pdb_id': '3f8y'},
{'experimental_method': ['X-ray diffraction'], 'pdb_id': '4m6l'},
{'experimental_method': ['X-ray diffraction'], 'pdb_id': '1kmv'},
{'experimental_method': ['X-ray diffraction'], 'pdb_id': '3nxy'},
{'experimental_method': ['X-ray diffraction'], 'pdb_id': '4g95'},
{'experimental_method': ['Solution NMR'], 'pdb_id': '1yho'},
{'experimental_method': ['X-ray diffraction'], 'pdb_id': '3nxv'},
{'experimental_method': ['X-ray diffraction'], 'pdb_id': '3l3r'},
{'experimental_method': ['X-ray diffraction'], 'pdb_id': '2c2s'},
{'experimental_method': ['X-ray diffraction'], 'pdb_id': '6a7c'},
{'experimental_method': ['X-ray diffraction'], 'pdb_id': '1u72'},
{'experimental_method': ['X-ray diffraction'], 'pdb_id': '5hsr'},
{'experimental_method': ['X-ray diffraction'], 'pdb_id': '1hfq'},
{'experimental_method': ['X-ray diffraction'], 'pdb_id': '5hqz'},
{'experimental_method': ['X-ray diffraction'], 'pdb_id': '3f8z'}]
We are going to use a Python package called Pandas to help us sort and visualise the results
First we have to do a bit of housekeeping, some of the results are lists (a PDB entry can have more than one experimental method or organism for example) so we need to change them into strings so we can use them in a graph
[11]:
def change_lists_to_strings(results):
"""
input - list of results from search
output - list of results with lists changed into strings
"""
for row in results:
for data in row:
if type(row[data]) == list:
# if there are any numbers in the list change them into strings
row[data] = [str(a) for a in row[data]]
# unique and sort the list and then change the list into a string
row[data] = ','.join(sorted(list(set(row[data]))))
return results
[12]:
results = change_lists_to_strings(results)
pprint(results)
[{'experimental_method': 'X-ray diffraction', 'pdb_id': '1boz'},
{'experimental_method': 'X-ray diffraction', 'pdb_id': '1pd8'},
{'experimental_method': 'X-ray diffraction', 'pdb_id': '6a7e'},
{'experimental_method': 'X-ray diffraction', 'pdb_id': '4kbn'},
{'experimental_method': 'X-ray diffraction', 'pdb_id': '4kd7'},
{'experimental_method': 'X-ray diffraction', 'pdb_id': '4qhv'},
{'experimental_method': 'X-ray diffraction', 'pdb_id': '1mvt'},
{'experimental_method': 'X-ray diffraction', 'pdb_id': '3ghv'},
{'experimental_method': 'X-ray diffraction', 'pdb_id': '3fs6'},
{'experimental_method': 'X-ray diffraction', 'pdb_id': '3ntz'},
{'experimental_method': 'X-ray diffraction', 'pdb_id': '3gyf'},
{'experimental_method': 'X-ray diffraction', 'pdb_id': '5ht4'},
{'experimental_method': 'X-ray diffraction', 'pdb_id': '2w3m'},
{'experimental_method': 'X-ray diffraction', 'pdb_id': '6de4'},
{'experimental_method': 'X-ray diffraction', 'pdb_id': '4m6j'},
{'experimental_method': 'X-ray diffraction', 'pdb_id': '5hui'},
{'experimental_method': 'X-ray diffraction', 'pdb_id': '5hqy'},
{'experimental_method': 'X-ray diffraction', 'pdb_id': '1hfp'},
{'experimental_method': 'X-ray diffraction', 'pdb_id': '4kfj'},
{'experimental_method': 'X-ray diffraction', 'pdb_id': '6dav'},
{'experimental_method': 'X-ray diffraction', 'pdb_id': '4keb'},
{'experimental_method': 'X-ray diffraction', 'pdb_id': '5hsu'},
{'experimental_method': 'X-ray diffraction', 'pdb_id': '4kak'},
{'experimental_method': 'X-ray diffraction', 'pdb_id': '4ddr'},
{'experimental_method': 'X-ray diffraction', 'pdb_id': '1hfr'},
{'experimental_method': 'X-ray diffraction', 'pdb_id': '3nxt'},
{'experimental_method': 'X-ray diffraction', 'pdb_id': '1pd9'},
{'experimental_method': 'X-ray diffraction', 'pdb_id': '1s3v'},
{'experimental_method': 'X-ray diffraction', 'pdb_id': '3s7a'},
{'experimental_method': 'X-ray diffraction', 'pdb_id': '5hpb'},
{'experimental_method': 'X-ray diffraction', 'pdb_id': '3s3v'},
{'experimental_method': 'X-ray diffraction', 'pdb_id': '1dlr'},
{'experimental_method': 'X-ray diffraction', 'pdb_id': '1dls'},
{'experimental_method': 'X-ray diffraction', 'pdb_id': '3nxo'},
{'experimental_method': 'X-ray diffraction', 'pdb_id': '3n0h'},
{'experimental_method': 'X-ray diffraction', 'pdb_id': '3eig'},
{'experimental_method': 'X-ray diffraction', 'pdb_id': '3nxx'},
{'experimental_method': 'X-ray diffraction', 'pdb_id': '1ohj'},
{'experimental_method': 'X-ray diffraction', 'pdb_id': '2dhf'},
{'experimental_method': 'X-ray diffraction', 'pdb_id': '5hvb'},
{'experimental_method': 'X-ray diffraction', 'pdb_id': '3nxr'},
{'experimental_method': 'X-ray diffraction', 'pdb_id': '1pdb'},
{'experimental_method': 'X-ray diffraction', 'pdb_id': '1drf'},
{'experimental_method': 'X-ray diffraction', 'pdb_id': '1mvs'},
{'experimental_method': 'X-ray diffraction', 'pdb_id': '1s3w'},
{'experimental_method': 'X-ray diffraction', 'pdb_id': '2c2t'},
{'experimental_method': 'X-ray diffraction', 'pdb_id': '3oaf'},
{'experimental_method': 'X-ray diffraction', 'pdb_id': '5ht5'},
{'experimental_method': 'X-ray diffraction', 'pdb_id': '3f91'},
{'experimental_method': 'X-ray diffraction', 'pdb_id': '3ghw'},
{'experimental_method': 'X-ray diffraction', 'pdb_id': '4qjc'},
{'experimental_method': 'X-ray diffraction', 'pdb_id': '3nu0'},
{'experimental_method': 'X-ray diffraction', 'pdb_id': '1kms'},
{'experimental_method': 'X-ray diffraction', 'pdb_id': '1u71'},
{'experimental_method': 'X-ray diffraction', 'pdb_id': '1dhf'},
{'experimental_method': 'X-ray diffraction', 'pdb_id': '3ghc'},
{'experimental_method': 'X-ray diffraction', 'pdb_id': '3nzd'},
{'experimental_method': 'X-ray diffraction', 'pdb_id': '2w3b'},
{'experimental_method': 'X-ray diffraction', 'pdb_id': '2w3a'},
{'experimental_method': 'X-ray diffraction', 'pdb_id': '3gi2'},
{'experimental_method': 'X-ray diffraction', 'pdb_id': '1ohk'},
{'experimental_method': 'X-ray diffraction', 'pdb_id': '4m6k'},
{'experimental_method': 'X-ray diffraction', 'pdb_id': '1s3u'},
{'experimental_method': 'X-ray diffraction', 'pdb_id': '5hve'},
{'experimental_method': 'X-ray diffraction', 'pdb_id': '3f8y'},
{'experimental_method': 'X-ray diffraction', 'pdb_id': '4m6l'},
{'experimental_method': 'X-ray diffraction', 'pdb_id': '1kmv'},
{'experimental_method': 'X-ray diffraction', 'pdb_id': '3nxy'},
{'experimental_method': 'X-ray diffraction', 'pdb_id': '4g95'},
{'experimental_method': 'Solution NMR', 'pdb_id': '1yho'},
{'experimental_method': 'X-ray diffraction', 'pdb_id': '3nxv'},
{'experimental_method': 'X-ray diffraction', 'pdb_id': '3l3r'},
{'experimental_method': 'X-ray diffraction', 'pdb_id': '2c2s'},
{'experimental_method': 'X-ray diffraction', 'pdb_id': '6a7c'},
{'experimental_method': 'X-ray diffraction', 'pdb_id': '1u72'},
{'experimental_method': 'X-ray diffraction', 'pdb_id': '5hsr'},
{'experimental_method': 'X-ray diffraction', 'pdb_id': '1hfq'},
{'experimental_method': 'X-ray diffraction', 'pdb_id': '5hqz'},
{'experimental_method': 'X-ray diffraction', 'pdb_id': '3f8z'}]
Notice that the only thing that changed is [‘X-ray diffraction’] is now ‘X-ray diffraction’
If we wanted to know the experimental methods used to determine structures of Human Dihydrofolate reductase we could loop through the results and count how many entries use each experimental method.
We can use a Python package called Pandas to do this for us. It changes the results into a mini database - called a DataFrame.
[13]:
def pandas_dataset(list_of_results):
results = change_lists_to_strings(list_of_results) # we have added our function to change lists to strings
df = pd.DataFrame(list_of_results)
return df
df = pandas_dataset(list_of_results=results)
print(df)
experimental_method pdb_id
0 X-ray diffraction 1boz
1 X-ray diffraction 1pd8
2 X-ray diffraction 6a7e
3 X-ray diffraction 4kbn
4 X-ray diffraction 4kd7
.. ... ...
74 X-ray diffraction 1u72
75 X-ray diffraction 5hsr
76 X-ray diffraction 1hfq
77 X-ray diffraction 5hqz
78 X-ray diffraction 3f8z
[79 rows x 2 columns]
We can use the this to count how many PDB codes there are for each experimental method This groups PDB IDs by experimental method and then counts the number of unique PDB IDs per method.
[14]:
ds = df.groupby('experimental_method')['pdb_id'].nunique()
print(ds)
experimental_method
Solution NMR 1
X-ray diffraction 78
Name: pdb_id, dtype: int64
We can find which experimental method has the greatest (max) or lowest (min) number of entries.
[15]:
dt = ds.max()
print(dt)
dt = ds.min()
print(dt)
78
1
We can sort the results so its in decending order and then the first value is the experimental method with the highest number of results
[16]:
ds.sort_values(ascending=False).index[0]
[16]:
'X-ray diffraction'
Or sort ascending so the experimental method with the lowest number of results is given
[17]:
ds.sort_values(ascending=True).index[0]
[17]:
'Solution NMR'
Or we can then very easily plot these results as a bar chart
[18]:
ds.iplot(kind='bar')
We will make this into two functions so we can resue them
[19]:
def pandas_count(list_of_results, column_to_group_by):
df = pandas_dataset(list_of_results)
ds = df.groupby(column_to_group_by)['pdb_id'].nunique()
return ds
def pandas_min_max(list_of_results, column_to_group_by, get_min=True):
df = pandas_dataset(list_of_results)
if get_min:
ds = df.groupby(column_to_group_by)['pdb_id'].min()
else:
ds = df.groupby(column_to_group_by)['pdb_id'].max()
return ds
def pandas_plot(list_of_results, column_to_group_by, graph_type='bar'):
ds = pandas_count(list_of_results=list_of_results, column_to_group_by=column_to_group_by)
ds.iplot(kind=graph_type)
One for counting the results
[20]:
pandas_count(list_of_results=results, column_to_group_by='experimental_method')
[20]:
experimental_method
Solution NMR 1
X-ray diffraction 78
Name: pdb_id, dtype: int64
One for getting min or max
[21]:
print('updated search')
search_terms = {"molecule_name":"Dihydrofolate reductase",
"organism_name":"Human"
}
filter_terms = ['pdb_id', 'resolution']
new_results = run_search(search_terms, filter_terms)
pandas_min_max(list_of_results=new_results, column_to_group_by='resolution')
updated search
https://www.ebi.ac.uk/pdbe/search/pdb/select?q=molecule_name:"Dihydrofolate reductase" AND organism_name:Human&fl=pdb_id,resolution&wt=json&rows=100
Number of results for Dihydrofolate reductase,Human: 79
[21]:
resolution
1.050 1kmv
1.090 1kms
1.201 4m6j
1.210 5hsr
1.230 3fs6
1.240 3ghw
1.270 2w3b
1.300 3ghc
1.350 3ntz
1.396 4m6k
1.400 2c2s
1.450 3f8y
1.460 5hqy
1.500 2c2t
1.530 3gi2
1.550 6dav
1.600 2w3m
1.610 4qhv
1.620 4qjc
1.650 5hpb
1.700 3eig
1.760 4kfj
1.800 1mvt
1.840 4kbn
1.850 6a7e
1.900 1mvs
1.920 3n0h
2.000 1drf
2.010 3f8z
2.050 4ddr
2.060 6a7c
2.100 1boz
2.200 1pd9
2.300 1dhf
2.411 6de4
2.500 1ohj
2.715 4kd7
Name: pdb_id, dtype: object
and one for plotting the results
[22]:
pandas_plot(list_of_results=results, column_to_group_by='experimental_method')
Remember this only searched through the first 10 results. To increase the number of entries we have to run the search again, this time setting number_of_rows to a number in the function run_search.
[23]:
search_terms = {"molecule_name":"Dihydrofolate reductase",
"organism_name":"Human"
}
results = run_search(search_terms, number_of_rows=10000)
https://www.ebi.ac.uk/pdbe/search/pdb/select?q=molecule_name:"Dihydrofolate reductase" AND organism_name:Human&wt=json&rows=10000
Number of results for Dihydrofolate reductase,Human: 79
Then we can count the results using our pandas function above
[24]:
pandas_count(list_of_results=results, column_to_group_by='experimental_method')
[24]:
experimental_method
Solution NMR 1
X-ray diffraction 78
Name: pdb_id, dtype: int64
Changing the result so it groups by release year of the PDB entries.
[25]:
pandas_count(list_of_results=results, column_to_group_by='release_year')
[25]:
release_year
1990 2
1992 1
1995 2
1998 6
2002 2
2003 5
2004 3
2005 3
2007 2
2009 13
2010 7
2011 7
2012 1
2013 8
2014 1
2015 2
2017 10
2018 2
2019 2
Name: pdb_id, dtype: int64
And then plot the number of entries released per year
[26]:
pandas_plot(list_of_results=results, column_to_group_by='release_year')
We can make this into a line graph
[27]:
pandas_plot(list_of_results=results, column_to_group_by='release_year', graph_type='line')
Try changing the term you want to search for and see if you get interesting results.
It would be interesting to see how many PDB entries were solved by each experimental method per year.
we can use the tag “release_year” to get the year of release of each entry
We have to define a new function to group entries by two terms.
When we do the search we have to filter the results by the terms we want to plot otherwise it takes too long to run.
[28]:
search_terms = {"all_enzyme_names":"Lysozyme",
}
filter_results = ['beam_source_name','release_year', 'pdb_id']
results = run_search(search_terms, filter_results, number_of_rows=10000)
https://www.ebi.ac.uk/pdbe/search/pdb/select?q=all_enzyme_names:Lysozyme&fl=beam_source_name,release_year,pdb_id&wt=json&rows=10000
Number of results for Lysozyme: 1913
This will take a while as it will return lots of results. We can then define a function to group the results by two terms.
[29]:
def pandas_plot_multi_groupby(results, first_column_to_group_by, second_column_to_group_by, y_axis='pdb_id', graph_type='line'):
df = pandas_dataset(results)
new_df = df.groupby([first_column_to_group_by, second_column_to_group_by])
ds = new_df.count().unstack().reset_index(first_column_to_group_by)
ds.iplot(x=first_column_to_group_by, y=y_axis, kind=graph_type)
def pandas_plot_multi_groupby_min(results, first_column_to_group_by, second_column_to_group_by, graph_type='line', use_min=False, use_max=False):
df = pandas_dataset(results)
new_df = df.groupby([first_column_to_group_by])[second_column_to_group_by]
ds = None
if use_min:
ds = new_df.min()
elif use_max:
ds = new_df.max()
else:
print('specify either use_min or use_max')
return None
ds.plot(x=first_column_to_group_by, y=second_column_to_group_by, kind=graph_type)
def pandas_box_plot(results, first_column_to_group_by, second_column_to_group_by):
df = pandas_dataset(results)
df.boxplot(column=second_column_to_group_by,by=first_column_to_group_by)
[30]:
pandas_plot_multi_groupby(results, 'release_year', 'beam_source_name')
This shows us that rotating anodes were used as the major source of radiation until around 2004 when Synchrotron’s overtook as the major source of radiation.
Try editing the queries to plot interesting trends within the PDB
Electron Microscopy is going through a revolution. Is this leading to a growth in Electron Microscopy PDB entries?
New refinement programs have got better and there are more methods to validate the quality of strucures in the PDB. Have structures got better over time? We can use “overall_quality” to judge this This could be plotted as a groupby or a box plot.
[ ]:
Electron Microscopy resolution has been said to be improving. Is this true? hint - the search term and filter can be different. pandas_plot_multi_groupby_min with use_min would be useful to plot this or maybe a box plot?
[ ]:
It has been said that all the simple structures have been done and that only complicated structures are left. One metric for “complicated” could be size of the assembly - assembly_mol_wt would be useful here.
[ ]: