Nature Communications (May 2021)
Exploring protein hotspots by optimized fragment pharmacophores
- Dávid Bajusz,
- Warren S. Wade,
- Grzegorz Satała,
- Andrzej J. Bojarski,
- Janez Ilaš,
- Jessica Ebner,
- Florian Grebien,
- Henrietta Papp,
- Ferenc Jakab,
- Alice Douangamath,
- Daren Fearon,
- Frank von Delft,
- Marion Schuller,
- Ivan Ahel,
- Amanda Wakefield,
- Sándor Vajda,
- János Gerencsér,
- Péter Pallai,
- György M. Keserű
Affiliations
- Dávid Bajusz
- Medicinal Chemistry Research Group, Research Centre for Natural Sciences
- Warren S. Wade
- BioBlocks, Inc.
- Grzegorz Satała
- Maj Institute of Pharmacology Polish Academy of Sciences
- Andrzej J. Bojarski
- Maj Institute of Pharmacology Polish Academy of Sciences
- Janez Ilaš
- Faculty of Pharmacy, University of Ljubljana
- Jessica Ebner
- Institute for Medical Biochemistry, University of Veterinary Medicine
- Florian Grebien
- Institute for Medical Biochemistry, University of Veterinary Medicine
- Henrietta Papp
- National Laboratory of Virology, Szentágothai Research Centre, University of Pécs
- Ferenc Jakab
- National Laboratory of Virology, Szentágothai Research Centre, University of Pécs
- Alice Douangamath
- Diamond Light Source Ltd., Harwell Science and Innovation Campus
- Daren Fearon
- Diamond Light Source Ltd., Harwell Science and Innovation Campus
- Frank von Delft
- Diamond Light Source Ltd., Harwell Science and Innovation Campus
- Marion Schuller
- Sir William Dunn School of Pathology, University of Oxford
- Ivan Ahel
- Sir William Dunn School of Pathology, University of Oxford
- Amanda Wakefield
- Department of Chemistry, Boston University
- Sándor Vajda
- Department of Chemistry, Boston University
- János Gerencsér
- BioBlocks, Inc.
- Péter Pallai
- BioBlocks, Inc.
- György M. Keserű
- Medicinal Chemistry Research Group, Research Centre for Natural Sciences
- DOI
- https://doi.org/10.1038/s41467-021-23443-y
- Journal volume & issue
-
Vol. 12,
no. 1
pp. 1 – 10
Abstract
Fragment-based drug discovery employs screening of small polar compounds typically exhibiting low affinity towards protein targets. Here, the authors combine the use of protein-based binding pharmacophores with the theory of protein hotspots to develop a design protocol for fragment libraries, called SpotXplorer, and validate their approach on common and emerging drug targets.
