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dc.contributor.authorHartono, Yossa Dwien
dc.contributor.authorXu, Youen
dc.contributor.authorKarshikoff, Andreyen
dc.contributor.authorNilsson, Lennarten
dc.contributor.authorVilla, Alessandraen
dc.identifier.citationHartono, Y. D., Xu, Y., Karshikoff, A., Nilsson, L., & Villa, A. (2018). Modeling pK shift in DNA triplexes containing locked nucleic acids. Journal of Chemical Information and Modeling, 58(4), 773-783. doi:10.1021/acs.jcim.7b00741en
dc.description.abstractThe protonation states for nucleic acid bases are difficult to assess experimentally. In the context of DNA triplex, the protonation state of cytidine in the third strand is particularly important, because it needs to be protonated in order to form Hoogsteen hydrogen bonds. A sugar modification, locked nucleic acid (LNA), is widely used in triplex forming oligonucleotides to target sites in the human genome. In this study, the parameters for LNA are developed in line with the CHARMM nucleic acid force field and validated toward the available structural experimental data. In conjunction, two computational methods were used to calculate the protonation state of the third strand cytidine in various DNA triplex environments: λ-dynamics and multiple pH regime. Both approaches predict pK of this cytidine shifted above physiological pH when cytidine is in the third strand in a triplex environment. Both methods show an upshift due to cytidine methylation, and a small downshift when the sugar configuration is locked. The predicted pK values for cytidine in DNA triplex environment can inform the design of better-binding oligonucleotides.en
dc.format.extent11 p.en
dc.relation.ispartofseriesJournal of Chemical Information and Modelingen
dc.rights© 2018 American Chemical Society. This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes.en
dc.subjectDNA Triplexesen
dc.subjectLocked Nucleic Acidsen
dc.subjectScience::Biological sciencesen
dc.titleModeling pK shift in DNA triplexes containing locked nucleic acidsen
dc.typeJournal Articleen
dc.contributor.schoolSchool of Biological Sciencesen
dc.description.versionPublished versionen
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