2026-10-12T15:03:27Z https://api.figshare.com/v2/oai

oai:figshare.com:article/33954486 2026-09-21T13:35:54Z category_1 category_4 category_13 category_14 category_873 category_734 category_64 portal_63 item_type_3 month_year_09_2026

Multifaceted Computational Analysis of O⁶‑Methylguanine and O⁶‑Methylthioguanine Nucleobase Complexes Michael C. Bowman (5297135) Kirsten M. Stinson (25083690) Biophysics Biochemistry Genetics Molecular Biology Chemical Sciences not elsewhere classified Biological Sciences not elsewhere classified Cancer two hydrogen bonds study probes deeper nucleobases likewise predicted nbo analyses demonstrated multifaceted computational analysis molecular electrostatic potential likewise highly mutagenic greater dispersion forces canonical base pairs energy decomposition analysis sapt2 +/ aug interaction energies computed interaction energy various forms unmethylated g theory revealed sulfur analog qualitatively similar pvdz levels prefer binding noticeably weaker noncovalent interactions mgmt ). less electrophilic left unchecked induces gc exocyclic amine driven primarily direct comparison bond donors >< sup Improper DNA methylation yields <i>O</i>⁶-methylguanine, which induces GC-AT mutations if left unchecked by <i>O</i>⁶-methylguanine DNA methyltransferase (MGMT). Previous ab initio studies have computed the interaction energy of <i>O</i>⁶-methylguanine with cytosine and thymine, but this study probes deeper by investigating the noncovalent interactions through various forms of energy decomposition analysis. The same methods are then applied to the sulfur analog of <i>O</i>⁶-methylguanine, <i>S</i>⁶-methylthioguanine, which is likewise highly mutagenic but has received considerably less computational treatment. Interaction energies computed at the ωB97X-D3/aug-cc-pVTZ and SAPT2+/aug-cc-pVDZ levels of theory revealed that <i>O</i>⁶-methylguanine and <i>S</i>⁶-methylthioguanine form substantially weaker complexes than the unmethylated G:C and TG:C pairs yet may continue to prefer binding to cytosine over thymine. NCI and NBO analyses demonstrated that the <i>O</i>⁶-methylguanine and <i>S</i>⁶-methylthioguanine complexes with cytosine or thymine are driven primarily by two hydrogen bonds, which are noticeably weaker than the average hydrogen bond observed among the canonical base pairs. The molecular electrostatic potential (MEP) of these nucleobases likewise predicted that the exocyclic amine on <i>O</i>⁶-methylguanine and <i>S</i>⁶-methylthioguanine is less electrophilic than the H-bond donors on guanine and thioguanine. In direct comparison to <i>O</i>⁶-methylguanine, the <i>S</i>⁶-methylthioguanine complexes are qualitatively similar but exhibit weaker hydrogen bonding and greater dispersion forces. 2026-09-21T00:00:00Z Dataset Dataset 10.1021/acs.jpcb.6c04517.s001 https://figshare.com/articles/dataset/Multifaceted_Computational_Analysis_of_O_sup_6_sup_Methylguanine_and_O_sup_6_sup_Methylthioguanine_Nucleobase_Complexes/33954486 CC BY-NC 4.0