Show simple item record

dc.contributor.authorSzatkowski, Lukasz
dc.contributor.authorLynn, Melissa L.
dc.contributor.authorHoleman, Teryn
dc.contributor.authorWilliams, Michael R.
dc.contributor.authorBaldo, Anthony P.
dc.contributor.authorTardiff, Jil C.
dc.contributor.authorSchwartz, Steven D.
dc.date.accessioned2019-10-23T18:24:43Z
dc.date.available2019-10-23T18:24:43Z
dc.date.issued2019-04-09
dc.identifier.citationSzatkowski, L., Lynn, M. L., Holeman, T., Williams, M. R., Baldo, A. P., Tardiff, J. C., & Schwartz, S. D. (2019). Proof of Principle that Molecular Modeling Followed by a Biophysical Experiment Can Develop Small Molecules that Restore Function to the Cardiac Thin Filament in the Presence of Cardiomyopathic Mutations. ACS Omega, 4(4), 6492-6501.en_US
dc.identifier.issn2470-1343
dc.identifier.doi10.1021/acsomega.8b03340
dc.identifier.urihttp://hdl.handle.net/10150/634793
dc.description.abstractThis article reports a coupled computational experimental approach to design small molecules aimed at targeting genetic cardiomyopathies. We begin with a fully atomistic model of the cardiac thin filament. To this we dock molecules using accepted computational drug binding methodologies. The candidates are screened for their ability to repair alterations in biophysical properties caused by mutation. Hypertrophic and dilated cardiomyopathies caused by mutation are initially biophysical in nature, and the approach we take is to correct the biophysical insult prior to irreversible cardiac damage. Candidate molecules are then tested experimentally for both binding and biophysical properties. This is a proof of concept study-eventually candidate molecules will be tested in transgenic animal models of genetic sarcomeric cardiomyopathies.en_US
dc.description.sponsorshipNIH [HL136375]en_US
dc.language.isoenen_US
dc.publisherAMER CHEMICAL SOCen_US
dc.rightsCopyright © 2019 American Chemical Society. This is an open access article published under an ACS Author Choice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes.en_US
dc.titleProof of Principle that Molecular Modeling Followed by a Biophysical Experiment Can Develop Small Molecules that Restore Function to the Cardiac Thin Filament in the Presence of Cardiomyopathic Mutationsen_US
dc.typeArticleen_US
dc.contributor.departmentUniv Arizona, Dept Meden_US
dc.contributor.departmentUniv Arizona, Dept Chem & Biochemen_US
dc.identifier.journalACS OMEGAen_US
dc.description.noteOpen access journalen_US
dc.description.collectioninformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.en_US
dc.eprint.versionFinal published versionen_US
dc.source.volume4
dc.source.issue4
dc.source.beginpage6492-6501
refterms.dateFOA2019-10-23T18:24:44Z


Files in this item

Thumbnail
Name:
acsomega.8b03340.pdf
Size:
3.650Mb
Format:
PDF
Description:
Final Published Version

This item appears in the following Collection(s)

Show simple item record