20.500.12556/DKUM-66666 Scaffold hopping and bioisosteric replacements based on binding site alignments Bioisosteric replacements and scaffold hopping play an important role in modern drug discovery and design, as they enable the change of either a core scaffold or substitutes in a drug structure, thereby facilitating optimization of pharmacokinetic properties and patenting, while the drug retains its activity. A new knowledge-based method was developed to obtain bioisosteric or scaffold replacements based on the extensive data existing in the Protein Data Bank. The method uses all-against-all ProBiS-based protein superimposition to identify ligand fragments that overlap in similar binding sites and could therefore be considered as bioisosteric replacements. The method was demonstrated on a specific example of drug candidate – a nanomolar butyrylcholinesterase inhibitor, on which bioisosteric replacements of the three ring fragments were performed. The new molecule containing bioisosteric replacements was evaluated virtually using AutoDock Vina; a similar score for the original and the compound with replacements was obtained, suggesting that the newly designed bioisostere compound might retain the potency of the original inhibitor. bioisosteres scaffold hopping protein alignment ProBiS drug design analysis methods matter structure modelling bioizosteri zamenjava skeleta poravnava proteinov ProBis racionalno načrtovanje učinkovin analizne metode struktura snovi modeliranje true false true Angleški jezik Slovenski jezik Znanstveno delo 2017-07-05 11:46:02 2017-07-05 11:46:54 2022-08-01 13:01:34 2019-07-11 15:54:54 2016 0 0 str. 2-7 št. 4 Letn. 89 Dec. 2016 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 0011-1643 543.2/.9 0011-1643 6066458 10.5562/cca2993 0011-1643 URN:SI:UM:DK:9O3KKKIB Croatica_Chemica_Acta_2016_Lesnik,_Konc,_Janezic_Scaffold_Hopping_and_Bioisosteric_Replacements_Based_on_Binding_Site_Alignments.pdf Croatica_Chemica_Acta_2016_Lesnik,_Konc,_Janezic_Scaffold_Hopping_and_Bioisosteric_Replacements_Based_on_Binding_Site_Alignments.pdf 1 4A8817398F7DC47689CF1CFBE5E92B4E 63f98193c9f3cbcc7f5092244d0dec1f98695afa2874bc4a530cefed7f43dc3f 5bae122e-7c0e-11eb-bb7a-00155d0001ca 20.500.12556/dkum/417e9b18-64f2-4159-a27a-441f311be5df https://dk.um.si/Dokument.php?lang=slv&id=113681 http://hrcak.srce.hr/171908 1 https://dk.um.si/Dokument.php?lang=slv&id=113680 Fakulteta za kemijo in kemijsko tehnologijo 0 0 0