{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Kobauri P"],"funding":["H2020 Marie Sklodowska-Curie Actions","Alexander von Humboldt-Stiftung","Center for Information Technology, University of Groningen","Dutch Research Council (NWO)"],"pagination":["4798-4817"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8958501"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["65(6)"],"pubmed_abstract":["Photopharmacology uses light to regulate the biological activity of drugs. This precise control is obtained through the incorporation of molecular photoswitches into bioactive molecules. A major challenge for photopharmacology is the rational design of photoswitchable drugs that show light-induced activation. Computer-aided drug design is an attractive approach toward more effective, targeted design. Herein, we critically evaluated different structure-based approaches for photopharmacology with <i>Escherichia coli</i> dihydrofolate reductase (eDHFR) as a case study. Through the iterative examination of our hypotheses, we progressively tuned the design of azobenzene-based, photoswitchable eDHFR inhibitors in five design-make-switch-test-analyze cycles. Targeting a hydrophobic subpocket of t"],"journal":["Journal of medicinal chemistry"],"pubmed_title":["Hypothesis-Driven, Structure-Based Design in Photopharmacology: The Case of eDHFR Inhibitors."],"pmcid":["PMC8958501"],"funding_grant_id":["713482","723.014.001"],"pubmed_authors":["Kobauri P","Maglia G","Kolarski D","Szymanski W","Schulte AM","Thallmair S","de Vries J","Galenkamp NS","Feringa BL","Simeth NA"],"additional_accession":[]},"is_claimable":false,"name":"Hypothesis-Driven, Structure-Based Design in Photopharmacology: The Case of eDHFR Inhibitors.","description":"Photopharmacology uses light to regulate the biological activity of drugs. This precise control is obtained through the incorporation of molecular photoswitches into bioactive molecules. A major challenge for photopharmacology is the rational design of photoswitchable drugs that show light-induced activation. Computer-aided drug design is an attractive approach toward more effective, targeted design. Herein, we critically evaluated different structure-based approaches for photopharmacology with <i>Escherichia coli</i> dihydrofolate reductase (eDHFR) as a case study. Through the iterative examination of our hypotheses, we progressively tuned the design of azobenzene-based, photoswitchable eDHFR inhibitors in five design-make-switch-test-analyze cycles. Targeting a hydrophobic subpocket of t","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Mar","modification":"2026-05-31T03:14:22.909Z","creation":"2024-11-05T18:22:17.415Z"},"accession":"S-EPMC8958501","cross_references":{"pubmed":["35258959"],"doi":["10.1021/acs.jmedchem.1c01962"]}}