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dc.contributor.authorValdés-Jiménez, Alejandro
dc.contributor.authorJiménez-González, Daniel
dc.contributor.authorKiper, Aytug K.
dc.contributor.authorRinné, Susanne
dc.contributor.authorDecher, Niels
dc.contributor.authorGonzález, Wendy
dc.contributor.authorReyes-Parada, Miguel
dc.contributor.authorNúñez-Vivanco, Gabriel
dc.date.accessioned2024-04-10T06:37:30Z
dc.date.available2024-04-10T06:37:30Z
dc.date.issued2022
dc.identifier10.3389/fphar.2022.855792
dc.identifier.issn16639812
dc.identifier.urihttps://hdl.handle.net/20.500.12728/11036
dc.description.abstractThe identification of similar three-dimensional (3D) amino acid patterns among different proteins might be helpful to explain the polypharmacological profile of many currently used drugs. Also, it would be a reasonable first step for the design of novel multitarget compounds. Most of the current computational tools employed for this aim are limited to the comparisons among known binding sites, and do not consider several additional important 3D patterns such as allosteric sites or other conserved motifs. In the present work, we introduce Geomfinder2.0, which is a new and improved version of our previously described algorithm for the deep exploration and discovery of similar and druggable 3D patterns. As compared with the original version, substantial improvements that have been incorporated to our software allow: (i) to compare quaternary structures, (ii) to deal with a list of pairs of structures, (iii) to know how druggable is the zone where similar 3D patterns are detected and (iv) to significantly reduce the execution time. Thus, the new algorithm achieves up to 353x speedup as compared to the previous sequential version, allowing the exploration of a significant number of quaternary structures in a reasonable time. In order to illustrate the potential of the updated Geomfinder version, we show a case of use in which similar 3D patterns were detected in the cardiac ions channels NaV1.5 and TASK-1. These channels are quite different in terms of structure, sequence and function and both have been regarded as important targets for drugs aimed at treating atrial fibrillation. Finally, we describe the in vitro effects of tafluprost (a drug currently used to treat glaucoma, which was identified as a novel putative ligand of NaV1.5 and TASK-1) upon both ion channels’ activity and discuss its possible repositioning as a novel antiarrhythmic drug. Copyright © 2022 Valdés-Jiménez, Jiménez-González, Kiper, Rinné, Decher, González, Reyes-Parada and Núñez-Vivanco.es_ES
dc.description.sponsorshipDICYT-USACH, (5392102RP-ACDicyt); Generalitat de Catalunya, (2017-SGR-1328, 2017-SGR-1414); Fondo Nacional de Desarrollo Científico y Tecnológico, FONDECYT, (1170662, 1191133); Ministerio de Economía y Competitividad, MINECO, (BES-2016-078046, SEV-2015-0493, TIN2015-65316-P)es_ES
dc.language.isoenes_ES
dc.publisherFrontiers Media S.A.es_ES
dc.subjectbinding site comparisonses_ES
dc.subjectbinding site similarityes_ES
dc.subjectcardiac ion channelses_ES
dc.subjectpolypharmacologyes_ES
dc.subjecttafluprostes_ES
dc.titleA New Strategy for Multitarget Drug Discovery/Repositioning Through the Identification of Similar 3D Amino Acid Patterns Among Proteins Structures: The Case of Tafluprost and its Effects on Cardiac Ion Channelses_ES
dc.typeArticlees_ES


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