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\n\nAll data were generated in-house at Leash Biosciences. We are providing roughly 98M training examples per protein, 200K validation examples per protein, and 360K test molecules per protein. To test generalizability, the test set contains building blocks that are not in the training set. These datasets are very imbalanced: roughly 0.5% of examples are classified as binders; we used 3 rounds of selection in triplicate to identify binders experimentally. Following the competition, Leash will make all the data available for future use (3 targets * 3 rounds of selection * 3 replicates * 133M molecules, or 3.6B measurements).
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\n\nBefore DEL Technology
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\n\nAfter DEL Technology
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Youtube - DNA-Encoded Libraries - A New Paradigm in Drug Design?
\n![](\"https://www.googleapis.com/download/storage/v1/b/kaggle-forum-message-attachments/o/inbox%2F761268%2Fe7b75829c51f092fbb0fcaa2ab6c3157%2FScreenshot%202024-04-08%20at%2010.36.26PM.png?generation=1712596024132412&alt=media\")
\n\nAll data were generated in-house at Leash Biosciences. We are providing roughly 98M training examples per protein, 200K validation examples per protein, and 360K test molecules per protein. To test generalizability, the test set contains building blocks that are not in the training set. These datasets are very imbalanced: roughly 0.5% of examples are classified as binders; we used 3 rounds of selection in triplicate to identify binders experimentally. Following the competition, Leash will make all the data available for future use (3 targets * 3 rounds of selection * 3 replicates * 133M molecules, or 3.6B measurements).
\n
\n\nBefore DEL Technology
\n
\n
\n\nAfter DEL Technology
\n
\n
Youtube - DNA-Encoded Libraries - A New Paradigm in Drug Design?
\n
i personally recommend hitgen video
\nhttps://www.youtube.com/watch?v=AVaYLHTwask
google for more
", "rawMarkdown": "i personally recommend hitgen video\nhttps://www.youtube.com/watch?v=AVaYLHTwask\n\ngoogle for more", "votes": 5, "replies": [ { "id": 2743115, "postDate": "2024-04-09T08:24:57.077Z", "content": "Thanks @hengck23 will update the topic
", "rawMarkdown": "Thanks @hengck23 will update the topic" } ] }, { "id": 2770404, "postDate": "2024-04-23T20:22:38.277Z", "content": "Here's (probably) a dumb question: for this competition, are we trying to predict if an individual compound/building block (buildingblockX_smiles) can bind to the protein or the structure of the fully assembled molecule (molecule_smiles)?
", "rawMarkdown": "Here's (probably) a dumb question: for this competition, are we trying to predict if an individual compound/building block (buildingblockX_smiles) can bind to the protein or the structure of the fully assembled molecule (molecule_smiles)?", "votes": 1, "replies": [ { "id": 2770568, "postDate": "2024-04-23T22:36:38.053Z", "content": "Fully assembled molecule (molecule_smiles) binds to the protein or not @joshuampatterson
", "rawMarkdown": "Fully assembled molecule (molecule_smiles) binds to the protein or not @joshuampatterson ", "replies": [ { "id": 2771876, "postDate": "2024-04-24T12:41:45.800Z", "content": "Thank you!!
", "rawMarkdown": "Thank you!!" } ] } ] }, { "id": 2758081, "postDate": "2024-04-17T23:37:20.080Z", "content": "Videos were really useful to develop a mental model of how DEL works. Thanks!
", "rawMarkdown": "Videos were really useful to develop a mental model of how DEL works. Thanks!", "votes": 1 }, { "id": 2741973, "postDate": "2024-04-08T17:14:18.877Z", "content": "How molecules don't bind? - dump question if anyone expert here to explain
", "rawMarkdown": "How molecules don't bind? - dump question if anyone expert here to explain", "replies": [ { "id": 2759166, "postDate": "2024-04-18T14:12:18.140Z", "content": "\n\nHow molecules don't bind? - dump question if anyone expert here to explain
\n
A common reason is the shape of the small mol doesn't fit in the receptor of the target protein. An analogy is to imagine a key and a lock, every receptor has a unique shape and there are molecules (and other proteins) that fit in and bind to the receptor and there are others that don't.
\nThere are other reasons as well (source GPT-4 for this part):
\nThere are several reasons why a molecule might not bind effectively to a target, such as a receptor, enzyme, or another molecule. Understanding these reasons is crucial in fields like pharmacology, where the effectiveness of drugs often depends on their ability to bind specific targets. Here are some key factors that might prevent a molecule from binding:
Structural Mismatch: The shape and size of the molecule must complement the target's binding site. If there is a poor geometric fit, the molecule may not be able to bind effectively.
\nChemical Incompatibility: The chemical properties of the molecule and the target site must be compatible. For example, opposite charges attract, so a negatively charged molecule might not bind well to a negatively charged binding site.
\nSteric Hindrance: Large or bulky groups on the molecule might interfere with binding by physically blocking the interaction with the target site.
\nCompetitive Binding: Other molecules might compete for the same binding site. If another molecule binds more strongly or is present in higher concentrations, it can outcompete the intended molecule for binding.
\nModification of Target or Molecule: Chemical modifications, such as phosphorylation or methylation, can alter the structure or charge of the target or the molecule, reducing binding affinity.
\nEnvironmental Factors: Conditions like pH, temperature, and ionic strength can affect the structure and binding dynamics of molecules and their targets.
\nDynamic Changes in Conformation: Proteins and other biological molecules often change shape, which can periodically hide or expose binding sites, affecting the ability of a molecule to bind consistently.
\nPresence of Inhibitors or Regulators: Some molecules are designed or naturally exist to prevent binding through various mechanisms, such as allosteric modulation where the binding of one molecule at a secondary site induces a conformational change that reduces affinity at the primary binding site.
Thank Your for your video suggestion.
", "rawMarkdown": "Thank Your for your video suggestion. ", "votes": 1 } ], "comments": [ { "id": 2742744, "author_name": "hengck23", "author_url": "", "post_date": "2024-04-09T03:53:20.593000", "content": "i personally recommend hitgen video
\nhttps://www.youtube.com/watch?v=AVaYLHTwask
google for more
", "votes": 5, "replies": [ { "id": 2743115, "author_name": "SeshuRaju 🧘♂️", "author_url": "", "post_date": "2024-04-09T08:24:57.077000", "content": "Thanks @hengck23 will update the topic
", "votes": 0, "replies": [] } ] }, { "id": 2770404, "author_name": "JoshuaMPatterson", "author_url": "", "post_date": "2024-04-23T20:22:38.277000", "content": "Here's (probably) a dumb question: for this competition, are we trying to predict if an individual compound/building block (buildingblockX_smiles) can bind to the protein or the structure of the fully assembled molecule (molecule_smiles)?
", "votes": 1, "replies": [ { "id": 2770568, "author_name": "SeshuRaju 🧘♂️", "author_url": "", "post_date": "2024-04-23T22:36:38.053000", "content": "Fully assembled molecule (molecule_smiles) binds to the protein or not @joshuampatterson
", "votes": 0, "replies": [ { "id": 2771876, "author_name": "JoshuaMPatterson", "author_url": "", "post_date": "2024-04-24T12:41:45.800000", "content": "Thank you!!
", "votes": 0, "replies": [] } ] } ] }, { "id": 2758081, "author_name": "Quang Nguyen", "author_url": "", "post_date": "2024-04-17T23:37:20.080000", "content": "Videos were really useful to develop a mental model of how DEL works. Thanks!
", "votes": 1, "replies": [] }, { "id": 2741973, "author_name": "SeshuRaju 🧘♂️", "author_url": "", "post_date": "2024-04-08T17:14:18.877000", "content": "How molecules don't bind? - dump question if anyone expert here to explain
", "votes": 0, "replies": [ { "id": 2759166, "author_name": "Matt Overing", "author_url": "", "post_date": "2024-04-18T14:12:18.140000", "content": "\n\nHow molecules don't bind? - dump question if anyone expert here to explain
\n
A common reason is the shape of the small mol doesn't fit in the receptor of the target protein. An analogy is to imagine a key and a lock, every receptor has a unique shape and there are molecules (and other proteins) that fit in and bind to the receptor and there are others that don't.
\nThere are other reasons as well (source GPT-4 for this part):
\nThere are several reasons why a molecule might not bind effectively to a target, such as a receptor, enzyme, or another molecule. Understanding these reasons is crucial in fields like pharmacology, where the effectiveness of drugs often depends on their ability to bind specific targets. Here are some key factors that might prevent a molecule from binding:
Structural Mismatch: The shape and size of the molecule must complement the target's binding site. If there is a poor geometric fit, the molecule may not be able to bind effectively.
\nChemical Incompatibility: The chemical properties of the molecule and the target site must be compatible. For example, opposite charges attract, so a negatively charged molecule might not bind well to a negatively charged binding site.
\nSteric Hindrance: Large or bulky groups on the molecule might interfere with binding by physically blocking the interaction with the target site.
\nCompetitive Binding: Other molecules might compete for the same binding site. If another molecule binds more strongly or is present in higher concentrations, it can outcompete the intended molecule for binding.
\nModification of Target or Molecule: Chemical modifications, such as phosphorylation or methylation, can alter the structure or charge of the target or the molecule, reducing binding affinity.
\nEnvironmental Factors: Conditions like pH, temperature, and ionic strength can affect the structure and binding dynamics of molecules and their targets.
\nDynamic Changes in Conformation: Proteins and other biological molecules often change shape, which can periodically hide or expose binding sites, affecting the ability of a molecule to bind consistently.
\nPresence of Inhibitors or Regulators: Some molecules are designed or naturally exist to prevent binding through various mechanisms, such as allosteric modulation where the binding of one molecule at a secondary site induces a conformational change that reduces affinity at the primary binding site.
Thank Your for your video suggestion.
", "votes": 1, "replies": [] } ], "raw_markdown_by_id": { "2741940": "# [Youtube - HitGen DEL Introduction](https://www.youtube.com/watch?v=AVaYLHTwask) shared by @hengck23 \n\n\n\n\n\n\n\n---\n\n# [Youtube - DNA-Encoded Libraries - A New Method of Hit Discovery](https://www.youtube.com/watch?v=2dnmRyl9G10&ab_channel=WuXiDiscoveryServices)\n\n\n\n\n\n---\n\n\n# - Combinations => 340 x 1,139 x 1,388 x 3 => 1,612,550,640 but 295,246,830 (train) + 1,674,896 (test) => 296,921,726 ( is only 18.4% of combinations !! )\n> All data were generated in-house at Leash Biosciences. We are providing roughly 98M training examples per protein, 200K validation examples per protein, and 360K test molecules per protein. To test generalizability, the test set contains building blocks that are not in the training set. These datasets are very imbalanced: roughly 0.5% of examples are classified as binders; **we used 3 rounds of selection in triplicate to identify binders experimentally. Following the competition, Leash will make all the data available for future use (3 targets * 3 rounds of selection * 3 replicates * 133M molecules, or 3.6B measurements)**.\n\n\n---\n\n\n# How protein (EPHX2, BRD4, ALB) will bind to generated molecules ? \n\n---\n# DEL Technology look like AI to Drug discovery \n> Before DEL Technology\n\n\n---\n\n> After DEL Technology\n\n\n## Single video answered many questions related to this competition. share interesting videos related to this competition.\n\n---\n[ Youtube - DNA-Encoded Libraries - A New Paradigm in Drug Design? ](https://www.youtube.com/watch?v=8jLIgTBJmdU&ab_channel=Amgen)\n\n\n", "2742744": "i personally recommend hitgen video\nhttps://www.youtube.com/watch?v=AVaYLHTwask\n\ngoogle for more", "2770404": "Here's (probably) a dumb question: for this competition, are we trying to predict if an individual compound/building block (buildingblockX_smiles) can bind to the protein or the structure of the fully assembled molecule (molecule_smiles)?", "2758081": "Videos were really useful to develop a mental model of how DEL works. Thanks!", "2741973": "How molecules don't bind? - dump question if anyone expert here to explain", "2768063": "", "2760838": "Thank Your for your video suggestion. " } }![](\"https://www.googleapis.com/download/storage/v1/b/kaggle-forum-message-attachments/o/inbox%2F761268%2Fe403d3b16874e19d6a2f05c87c7b3b75%2FScreenshot%202024-04-08%20at%2010.22.32PM.png?generation=1712595208624576&alt=media\")
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