{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["6(1)"],"submitter":["Noori Z"],"pubmed_abstract":["Expanding the genetic alphabet requires a mechanistic understanding of how synthetic bases are faithfully replicated alongside natural DNA. We present a quantum chemical study reproducing the experimentally observed single-nucleotide incorporation selectivity of Hirao's unnatural base pairs (UBPs) by the 3'-5' exonuclease-deficient Klenow fragment of <i>Escherichia coli</i> DNA polymerase I. Our analysis focuses on the highly selective DsPx pair, benchmarking its behavior against canonical Watson-Crick pairs and other UBPs. Strikingly, the observed selectivity emerges without explicitly modeling the polymerase, relying solely on computed stacking energies within the DNA helix. Molecular orbital and energy-decomposition analyses show that both electrostatic and dispersion interactions stren"],"journal":["ACS physical chemistry Au"],"pagination":["153-162"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12856653"],"repository":["biostudies-literature"],"pubmed_title":["π-π Stacking Determines the Selectivity of Unnatural DNA Base Pairs Even without Polymerase."],"pmcid":["PMC12856653"],"pubmed_authors":["Bofill JM","Poater J","Noori Z","Bermejo A"],"additional_accession":[]},"is_claimable":false,"name":"π-π Stacking Determines the Selectivity of Unnatural DNA Base Pairs Even without Polymerase.","description":"Expanding the genetic alphabet requires a mechanistic understanding of how synthetic bases are faithfully replicated alongside natural DNA. We present a quantum chemical study reproducing the experimentally observed single-nucleotide incorporation selectivity of Hirao's unnatural base pairs (UBPs) by the 3'-5' exonuclease-deficient Klenow fragment of <i>Escherichia coli</i> DNA polymerase I. Our analysis focuses on the highly selective DsPx pair, benchmarking its behavior against canonical Watson-Crick pairs and other UBPs. Strikingly, the observed selectivity emerges without explicitly modeling the polymerase, relying solely on computed stacking energies within the DNA helix. Molecular orbital and energy-decomposition analyses show that both electrostatic and dispersion interactions stren","dates":{"release":"2026-01-01T00:00:00Z","publication":"2026 Jan","modification":"2026-06-18T05:49:12.14Z","creation":"2026-06-18T03:07:36.353Z"},"accession":"S-EPMC12856653","cross_references":{"pubmed":["41624708"],"doi":["10.1021/acsphyschemau.5c00100"]}}