{"id":9608,"date":"2023-04-10T17:51:02","date_gmt":"2023-04-10T16:51:02","guid":{"rendered":"https:\/\/www.blopig.com\/blog\/?p=9608"},"modified":"2023-04-18T16:23:58","modified_gmt":"2023-04-18T15:23:58","slug":"brics-decomposition-in-3d","status":"publish","type":"post","link":"https:\/\/www.blopig.com\/blog\/2023\/04\/brics-decomposition-in-3d\/","title":{"rendered":"BRICS Decomposition in 3D"},"content":{"rendered":"\n

Inspired by this blog post<\/a> by the lovely Kate, I’ve been doing some BRICS decomposing of molecules myself. Like the structure-based goblin that I am, though, I’ve been applying it to 3D structures of molecules, rather than using the smiles approach she detailed. I thought it may be helpful to share the code snippets I’ve been using for this: unsurprisingly, it can also be done with RDKit!<\/p>\n\n\n\n

I’ll use the same example as in the original blog post, propranolol.<\/p>\n\n\n

\n
\"\"<\/a>
1DY4<\/a>: CBH1 IN COMPLEX WITH S-PROPRANOLOL<\/em><\/figcaption><\/figure>\n<\/div>\n\n\n

First, I import RDKit and load the ligand in question:<\/p>\n\n\n\n\n\n\n\n

from rdkit import Chem\nfrom rdkit.Chem import AllChem\nfrom rdkit.Chem import BRICS\nligand = Chem.MolFromMolFile('propranolol.sdf')<\/pre>\n\n\n\n
Then I use BRICS.BreakBRICSBonds to generate an RDKit molecule with the BRICS bonds removed, and then Chem.GetMolFrags to separate the substructures into individual RDKit molecules:<\/p>\n\n\n\n
ligand_broken = BRICS.BreakBRICSBonds(ligand)\nbrics_bits = Chem.GetMolFrags(ligand_broken, asMols=True)<\/pre>\n\n\n\n
You can either write these directly to SDF files using Chem.SDWriter, or remove the dummy atoms first. I followed this post<\/a> to do this as follows:<\/p>\n\n\n\n
w = Chem.SDWriter('propranolol_brics.sdf')\ndummy = Chem.MolFromSmiles('*')\nhydrogen = Chem.MolFromSmiles('[H]')\nfor mol in brics_bits:\n    for atom in mol.GetAtoms():\n        atom.SetIsotope(0)\n    \n    rmv_dummy = AllChem.ReplaceSubstructs(mol,dummy,hydrogen,True)[0]\n    final_mol = Chem.RemoveHs(rmv_dummy)\n\n\n    w.write(final_mol)\n<\/pre>\n\n\n\n
The final molecules loaded into PyMOL look like this:<\/p>\n\n\n
\n
\"\"<\/a>
BRICS decomposition applied to propranolol in 3D<\/em><\/figcaption><\/figure>\n<\/div>\n\n\n
Happy decomposing!<\/p>\n","protected":false},"excerpt":{"rendered":"
Inspired by this blog post by the lovely Kate, I’ve been doing some BRICS decomposing of molecules myself. Like the structure-based goblin that I am, though, I’ve been applying it to 3D structures of molecules, rather than using the smiles approach she detailed. I thought it may be helpful to share the code snippets I’ve […]<\/p>\n","protected":false},"author":94,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"nf_dc_page":"","wikipediapreview_detectlinks":true,"_monsterinsights_skip_tracking":false,"_monsterinsights_sitenote_active":false,"_monsterinsights_sitenote_note":"","_monsterinsights_sitenote_category":0,"ngg_post_thumbnail":0,"_jetpack_memberships_contains_paid_content":false,"footnotes":""},"categories":[14,227,201],"tags":[129,134],"ppma_author":[559],"class_list":["post-9608","post","type-post","status-publish","format-standard","hentry","category-howto","category-python-code","category-small-molecules","tag-rdkit","tag-small-molecules"],"jetpack_featured_media_url":"","jetpack_sharing_enabled":true,"authors":[{"term_id":559,"user_id":94,"is_guest":0,"slug":"lucy_vost","display_name":"Lucy Vost","avatar_url":"https:\/\/secure.gravatar.com\/avatar\/410b510f70dab77a9fa285069d544f6f8069c1743e6050067edc992e470b551e?s=96&d=mm&r=g","0":null,"1":"","2":"","3":"","4":"","5":"","6":"","7":"","8":""}],"_links":{"self":[{"href":"https:\/\/www.blopig.com\/blog\/wp-json\/wp\/v2\/posts\/9608","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.blopig.com\/blog\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.blopig.com\/blog\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.blopig.com\/blog\/wp-json\/wp\/v2\/users\/94"}],"replies":[{"embeddable":true,"href":"https:\/\/www.blopig.com\/blog\/wp-json\/wp\/v2\/comments?post=9608"}],"version-history":[{"count":3,"href":"https:\/\/www.blopig.com\/blog\/wp-json\/wp\/v2\/posts\/9608\/revisions"}],"predecessor-version":[{"id":9659,"href":"https:\/\/www.blopig.com\/blog\/wp-json\/wp\/v2\/posts\/9608\/revisions\/9659"}],"wp:attachment":[{"href":"https:\/\/www.blopig.com\/blog\/wp-json\/wp\/v2\/media?parent=9608"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.blopig.com\/blog\/wp-json\/wp\/v2\/categories?post=9608"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.blopig.com\/blog\/wp-json\/wp\/v2\/tags?post=9608"},{"taxonomy":"author","embeddable":true,"href":"https:\/\/www.blopig.com\/blog\/wp-json\/wp\/v2\/ppma_author?post=9608"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}