{"doi":"10.1039/d1sc00163a","title":"DeepFrag: a deep convolutional neural network for fragment-based lead optimization","abstract":"Machine learning has been increasingly applied to the field of computer-aided drug discovery in recent years, leading to notable advances in binding-affinity prediction, virtual screening, and QSAR. Surprisingly, it is less often applied to lead optimization, the process of identifying chemical fragments that might be added to a known ligand to improve its binding affinity. We here describe a deep convolutional neural network that predicts appropriate fragments given the structure of a receptor/ligand complex. In an independent benchmark of known ligands with missing (deleted) fragments, our DeepFrag model selected the known (correct) fragment from a set over 6500 about 58% of the time. Even when the known/correct fragment was not selected, the top fragment was often chemically similar and may well represent a valid substitution. We release our trained DeepFrag model and associated software under the terms of the Apache License, Version 2.0.","journal":"Chemical Science","year":2021,"id":149647,"datarank":0.6966586348712059,"base_score":4.6443908991413725,"endowment":4.6443908991413725,"self_citation_contribution":0.6966586348712059,"citation_network_contribution":0.0,"self_endowment_contribution":0.6966586348712059,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":103,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9494,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":36750,"name":"David Ryan Koes","orcid":"0000-0002-6892-6614","position":1,"is_corresponding":false},{"id":71084,"name":"Jacob D. Durrant","orcid":"0000-0002-5808-4097","position":2,"is_corresponding":false},{"id":636452,"name":"Harrison Green","orcid":"0000-0003-3986-3906","position":0,"is_corresponding":true}],"reference_count":41,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:42:56.251607Z","pmid":"34194693","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}