SantaLucia 1998 — Unified nearest-neighbor thermodynamics for DNA
Full citation: SantaLucia J Jr. “A unified view of polymer, dumbbell, and oligonucleotide DNA nearest-neighbor thermodynamics.” Proc Natl Acad Sci USA. 1998 Feb 17;95(4):1460-5. PMID 9465037.
Numbers that matter
Unified nearest-neighbor ΔH (kcal/mol) and ΔS (cal/mol/K) parameters for all 10 unique DNA:DNA dinucleotide pairs (1 M NaCl, 0.2 µM oligonucleotide):
| Dinucleotide (5’→3’) | ΔH (kcal/mol) | ΔS (cal/mol/K) |
|---|---|---|
| AA/TT | −7.9 | −22.2 |
| AT/TA | −7.2 | −20.4 |
| TA/AT | −7.2 | −21.3 |
| CA/GT | −8.5 | −22.7 |
| GT/CA | −8.4 | −22.4 |
| CT/GA | −7.8 | −21.0 |
| GA/CT | −8.2 | −22.2 |
| CG/GC | −10.6 | −27.2 |
| GC/CG | −9.8 | −24.4 |
| GG/CC | −8.0 | −19.9 |
Initiation parameters: ΔH_init = 0.2 kcal/mol, ΔS_init = −5.7 cal/mol/K (for oligomers with terminal GC).
Tm formula: Tm = (1000 × ΔH) / (ΔS + R × ln(C_T/4)) − 273.15 (for non-self-complementary duplexes), with salt correction 16.6 × log10([Na+]).
Usage in STRC vault
aso_phase1_design.py(h08):NN_dHandNN_dSdictionaries embedded in script exactly match the published table above. The script applies these as DNA:RNA proxy (appropriate for relative ranking). ✅- h08 audit (2026-04-23) stated “values match published SantaLucia 1998 unified parameters exactly (e.g., AA: dH=-7.9, dS=-22.2; CG: dH=-10.6, dS=-27.2).” Independently confirmed 2026-04-25. ✅
Notes
- The 108-oligonucleotide training set gives R² > 0.98 between predicted and measured Tm across a wide range.
- SantaLucia 1998 supersedes the earlier 7-parameter set (SantaLucia et al. 1996). The unified set is the current gold standard.
- Applying DNA:DNA parameters as proxy for DNA:RNA hybrid Tm introduces ~1-3°C systematic bias (RNA:DNA hybrids are slightly more stable). Acceptable for relative ranking; insufficient for absolute Tm prediction of ASO–mRNA hybrids.
Connections
[applies]STRC ASO Exon Skipping (h08)[source]STRC ASO Phase1 Splice-Switch Design